Co-reporter:Teng Chen;Xingchu Gong;Huali Chen;Ying Zhang
Journal of Separation Science 2016 Volume 39( Issue 2) pp:306-315
Publication Date(Web):
DOI:10.1002/jssc.201500976
A Monte Carlo method was used to develop the design space of a chromatographic elution process for the purification of saponins in Panax notoginseng extract. During this process, saponin recovery ratios, saponin purity, and elution productivity are determined as process critical quality attributes, and ethanol concentration, elution rate, and elution volume are identified as critical process parameters. Quadratic equations between process critical quality attributes and critical process parameters were established using response surface methodology. Then probability-based design space was computed by calculating the prediction errors using Monte Carlo simulations. The influences of calculation parameters on computation results were investigated. The optimized calculation condition was as follows: calculation step length of 0.02, simulation times of 10 000, and a significance level value of 0.15 for adding or removing terms in a stepwise regression. Recommended normal operation region is located in ethanol concentration of 65.0–70.0%, elution rate of 1.7–2.0 bed volumes (BV)/h and elution volume of 3.0–3.6 BV. Verification experiments were carried out and the experimental values were in a good agreement with the predicted values. The application of present method is promising to develop a probability-based design space for other botanical drug manufacturing process.
Co-reporter:Lu Wang, Shanshan Zeng, Haibin Qu
Journal of Pharmaceutical and Biomedical Analysis 2016 Volume 121() pp:30-38
Publication Date(Web):20 March 2016
DOI:10.1016/j.jpba.2016.01.001
•18 bioactive compounds of six species were analyzed under different DART operating parameters.•DART-MS analytical results were evaluated by peak area and S/N of the characteristic ion signals.•The relationships among compounds, DART conditions and analytical responses were clarified.•Adequate ion source operating parameters were proposed for types of TCM active substance.Direct analysis in real time mass spectrometry (DART-MS) provides a new analytical method for traditional Chinese medicine (TCM). The present study investigated the effects of key ion source operating parameters on DART-MS analysis of various TCM active components. A total of 18 active components, including phenylpropanoids, alkaloids, saponins, flavones, volatile oils, and glycosides, were examined. For each substance, the peak area and signal-to-noise of its characteristic ions under different reagent gases and heater temperatures were compared. Based on the comparison, the relationships among chemical structures, ion source parameters and instrument responses were revealed. Finally, some suggestions about choosing reagent gas and heater temperature were proposed for types of TCM active substance, which offered a reference for the application of DART-MS on TCM analysis.
Co-reporter:Xingchu Gong, Ying Zhang, Huali Chen, Teng Chen, Jianyang Pan, Xiaoyu Wang and Haibin Qu
Analytical Methods 2016 vol. 8(Issue 10) pp:2282-2289
Publication Date(Web):11 Feb 2016
DOI:10.1039/C5AY03119B
A reversed-phase HPLC-UV method was developed using a design space approach for the simultaneous determination of five saponins in the extracts of Panax notoginseng, which were notoginsenoside R1, ginsenosides Rg1, Re, Rb1, and Rd. In the development of this method, resolutions of three critical peak pairs were considered as critical quality attributes (CQAs). The effects of four parameters on gradient elution were quantitatively investigated. Design space with a probability to attain CQA criteria higher than 0.9 was calculated using a Monte-Carlo simulation method. Several gradients were optimized in this work. The newly developed method was validated and can be used for saponin concentration determination of Panax notoginseng extracts.
Co-reporter:Wenlong Li, Haibin Qu
Chemometrics and Intelligent Laboratory Systems 2016 Volume 152() pp:140-145
Publication Date(Web):15 March 2016
DOI:10.1016/j.chemolab.2015.12.018
Near infrared spectroscopy combined with chemometrics was investigated for the fast determination of total organic carbon (TOC) and soluble solids contents (SSC) of Tanreqing injection intermediates. The NIR spectra were collected in transflective mode, and the TOC and SSC reference values were determined with Multi N/C UV HS analyzer and loss on drying method. The samples were divided into calibration sets and validation sets using the Kennard–Stone (KS) algorithm. The Dixon test, leverage and studentized residual test were studied for the sample outlier analysis. The selection of wavebands, spectra pretreated method and the number of latent variables were optimized to obtain better results. The quantitative calibration models were established with 3 different PLS regression algorithms, named linear PLS, non-linear PLS and concentration weighted PLS, and the net result was defined as the average of the predicted values of the different calibration models. The overall results indicated that the presented method is more powerful than single multivariable regression method, characterized by higher mean recovery rate (MRR) of the validation set, and can be used for the rapid determination of TOC and SSC values of Tanreqing injection intermediates, which are two important quality indicators for the process monitoring.
Co-reporter:Xingchu Gong, Shichao Huang, Ruonan Jiao, Jianyang Pan, Yao Li, Haibin Qu
Fluid Phase Equilibria 2016 Volume 409() pp:447-457
Publication Date(Web):15 February 2016
DOI:10.1016/j.fluid.2015.11.004
A liquid–liquid equilibrium method to determine dissociation constants was presented in this work using phenolic acids in the water extract of Salvia miltiorrhiza as a sample. The models to quantitatively describe the relationship between aqueous phase pH value and apparent distribution coefficient value were built. Apparent distribution coefficients are determined after liquid–liquid equilibrium experiments. The pKa values of phenolic acids in S. miltiorrhiza extracts were fitted successfully. The dissociation constants of active ingredients that are in a mixture in which most components are unknown can be determined using this method. The distribution coefficients of active ingredient molecules and ions can also be obtained. 1-Octanol is a recommended solvent with low solubility, high boiling point, and extra information of Kow.
Co-reporter:Wen-long Li;Hai-fan Han;Lu Zhang;Yan Zhang
Journal of Zhejiang University-SCIENCE B 2016 Volume 17( Issue 5) pp:382-390
Publication Date(Web):2016 May
DOI:10.1631/jzus.B1500186
We have developed a set of chemometric methods to address two critical issues in quality control of a precious traditional Chinese medicine (TCM), Dong’e Ejiao (DEEJ). Based on near infrared (NIR) spectra of multiple samples, the genuine manufacturer of DEEJ, e.g. Dong’e Ejiao Co., Ltd., was accurately identified among 21 suppliers by the fingerprint method using Hotelling T2, distance to Model X (DModX), and similarity match value (SMV) as discriminate criteria. Soft independent modeling of the class analogy algorithm led to a misjudgment ratio of 6.2%, suggesting that the fingerprint method is more suitable for manufacturer identification. For another important feature related to clinical efficacy of DEEJ, storage time, the partial least squares-discriminant analysis (PLS-DA) method was applied with a satisfactory misjudgment ratio (15.6%) and individual prediction error around 1 year. Our results demonstrate that NIR spectra comprehensively reflect the essential quality information of DEEJ, and with the aid of proper chemometric algorithms, it is able to identify genuine manufacturer and determine accurate storage time. The overall results indicate the promising potential of NIR spectroscopy as an effective quality control tool for DEEJ and other precious TCM products.对东阿阿胶的生产厂家和存放时间进行鉴定,为 东阿阿胶的品牌保护和质量控制提供技术手段。首次报道采用近红外光谱指纹图谱技术和相关的 化学计量学方法对东阿阿胶进行质量控制。收集有代表性的阿胶样品,其中包括来自不同厂 家的阿胶、黄明胶、龟甲胶、鹿角胶样品188 份 和来自东阿阿胶股份有限公司2005~2012 年间生 产的阿胶,每年30 批,共计240 份东阿阿胶样品。 采集样品光谱,采用Hotelling T2、DModX 和相 似度匹配值等统计量作为判断标准,进行东阿阿 胶品牌的鉴定; 采用偏最小二乘判别分析 (PLS-DA)方法进行东阿阿胶存放年限的判别 分析。所建立的方法可有效区分东阿阿胶与黄明胶、龟 甲胶、鹿角胶、以及其他品牌的阿胶,可用于东 阿阿胶的品牌保护;利用PLS-DA 可对不同存放 年限的东阿阿胶进行判别分析,结果令人满意。
Co-reporter:Lu Wang
Analytical and Bioanalytical Chemistry 2016 Volume 408( Issue 8) pp:2133-2145
Publication Date(Web):2016 March
DOI:10.1007/s00216-016-9316-3
A method combining solid phase extraction, high performance liquid chromatography, and ultraviolet/evaporative light scattering detection (SPE-HPLC-UV/ELSD) was developed according to Quality by Design (QbD) principles and used to assay nine bioactive compounds within a botanical drug, Shenqi Fuzheng Injection. Risk assessment and a Plackett–Burman design were utilized to evaluate the impact of 11 factors on the resolutions and signal-to-noise of chromatographic peaks. Multiple regression and Pareto ranking analysis indicated that the sorbent mass, sample volume, flow rate, column temperature, evaporator temperature, and gas flow rate were statistically significant (p < 0.05) in this procedure. Furthermore, a Box–Behnken design combined with response surface analysis was employed to study the relationships between the quality of SPE-HPLC-UV/ELSD analysis and four significant factors, i.e., flow rate, column temperature, evaporator temperature, and gas flow rate. An analytical design space of SPE-HPLC-UV/ELSD was then constructed by calculated Monte Carlo probability. In the presented approach, the operating parameters of sample preparation, chromatographic separation, and compound detection were investigated simultaneously. Eight terms of method validation, i.e., system-suitability tests, method robustness/ruggedness, sensitivity, precision, repeatability, linearity, accuracy, and stability, were accomplished at a selected working point. These results revealed that the QbD principles were suitable in the development of analytical procedures for samples in complex matrices. Meanwhile, the analytical quality and method robustness were validated by the analytical design space. The presented strategy provides a tutorial on the development of a robust QbD-compliant quantitative method for samples in complex matrices.
Co-reporter:Wenlong Li, Haifan Han, Zhiwei Cheng, Yan Zhang, Shaoyong Liu, Haibin Qu
Sensors and Actuators B: Chemical 2016 Volume 231() pp:313-323
Publication Date(Web):August 2016
DOI:10.1016/j.snb.2016.03.023
•In-line NIR combined with MSPC is presented for the real-time batch process monitoring.•Two representative TCM technical processes were taken as examples.•Three kinds of control charts were used to monitor the test batches with artificial variations.•NIR-based multivariate process trajectories were proposed for the TCM manufacture.Traditional Chinese medicine (TCM) products are usually manufactured through batch processes. To improve the batch-to-batch reproducibility, practical approaches for the real-time monitoring of batch evolution need to be developed. In-line near-infrared (NIR) spectroscopy combined with multivariate statistical process control (MSPC) method, as an efficient process analytical technology, is presented for the real-time batch process monitoring. Two representative TCM technical processes, the alkaline precipitation of the compound E-Jiao oral liquid and the liquid preparation process of Tanreqing injection, were taken as examples. The NIR spectra collected in-line was “variable-wise” unfolded into two-dimensional matrix, and multi-way principal component analysis (MPCA) model were developed based on the rearranged data of the normal operation condition (NOC) batches. Three kinds of multivariate control charts (PC scores, Hotelling T2 and DModX) were used to monitor the evolution of test batches with artificial batch variations, including the change of starting material quality attributes and abnormal operation conditions. As illustrated with test batches, the established model can identify NOC or AOC (abnormal operation condition) batches accurately, and detect different kinds of deviations from NOC batches using these control charts. The results indicated that the NIR-based multivariate process trajectories can reflect the batch-to-batch reproducibility effectively, and can also help for the diagnosis of the failure batches in the TCM production.
Co-reporter:Teng Chen;Xingchu Gong;Huali Chen
Journal of Separation Science 2015 Volume 38( Issue 2) pp:346-355
Publication Date(Web):
DOI:10.1002/jssc.201400808
A systematic, yet simple method for the decoloration of Panax notoginseng extracts has been developed by static adsorption tests and response surface methodology. Through static adsorption experiment screening, acidic alumina was selected because of its high decoloration ratio and saponin recovery ratios. Using response surface methodology, the correlation between the process parameters (i.e., sample volume and flow rate) and decoloration performance was modeled. A design space of the decoloration process was subsequently established through the proposed models. The verification experimental values were in good agreement with the predicted values. The design space was proven reliable, because all the verification experimental results attained the criteria for design space development. Moreover, most of the saponins adsorbed by the acidic alumina could be recovered through dynamic desorption using water and ethanol. The method developed in the current study is highly efficient, flexible, and easy to control, thus providing a promising approach for the decoloration of Panax notoginseng extracts with consistent decoloration performance.
Co-reporter:Cheng Jiang, Haibin Qu
Journal of Pharmaceutical and Biomedical Analysis 2015 Volume 102() pp:78-84
Publication Date(Web):5 January 2015
DOI:10.1016/j.jpba.2014.08.029
•Comparative evaluation of using NIR, UV and fused spectra was conducted.•UVE-PLS regression models were established for quantification of five saponins.•There was a significant improvement provided by models based on fused spectra.•The fusion method was a promising strategy for real-time analysis of saponins.The step of enriching and purifying saponins by macroporous resin column chromatography is closely related to the safety and efficacy of Panax notoginseng products during their manufacturing processes. Adsorption process is one of the most critical unit operations within each chromatographic cycle. In order to understand the adsorption process directly, it is necessary to develop a rapid and precise method to monitor the adsorption process in real time. In this study, comparative evaluation of using near-infrared (NIR) spectra, ultraviolet (UV) spectra and fused spectra to monitor the adsorption process of P. notoginseng was conducted. The uninformative variable elimination by partial least squares (UVE-PLS) regression models were established for quantification of notoginsenoside R1, ginsenoside Rg1, ginsenoside Re, ginsenoside Rb1 and ginsenoside Rd in effluents based on different spectra. There was a significant improvement provided by the models based on fused spectra. The results in this work were conducive to solving the problems about real-time quantitative analysis of saponins during P. notoginseng adsorption. The fusion method of NIR and UV spectra combined with UVE-PLS regression could be a promising strategy to real-time analyze the components, which are difficult to be quantified by individual spectroscopic technique.Compared with the models based on independent NIR or UV spectra, there was a significant improvement provided by the models based on fused spectra.
Co-reporter:Teng Chen, Xingchu Gong, Ying Zhang, Huali Chen, Haibin Qu
Separation and Purification Technology 2015 Volume 154() pp:309-319
Publication Date(Web):5 November 2015
DOI:10.1016/j.seppur.2015.09.035
•Loss mechanism of botanical active ingredients in wash step of a chromatographic process was investigated.•Design space based on probability is calculated using a Monte-Carlo method.•The chromatographic process was optimized considering drug effectiveness, drug safety, and process efficiency.Quality by Design principle was applied to optimize the load and wash steps in the chromatographic process of Panax notoginseng extracts. Saponin recovery, saponin purity and saponin yield per unit volume of resin were identified as the process critical quality attributes (CQAs) of the chromatographic process. The critical process parameters (CPPs) were determined by an Ishikawa diagram combined with a Failure Mode and Effect Analysis. Column height/diameter ratio, load rate, load volume, total saponin concentration in loading solution and wash volume were identified as CPPs for the load and wash steps. The models between CPPs and process CQAs were developed according to the data obtained from central composite designed experiments. Determination coefficients (R2) were higher than 0.83 for all the models. Loss mechanism of saponins was discussed, overloading may lead to the loss of all the saponins and wash with water may lead to the loss of notoginsenoside R1, ginsenoside Rg1 and ginsenoside Re. Design spaces with different acceptable probabilities were calculated using a Monte-Carlo simulation method. Recommended normal operation region is located in height/diameter ratio of 13.5–15.0, load rate of 1.5–1.6 BV/h, load volume of 5.5–6.0 BV, total saponin concentration of 10.4–12.2 mg/g, wash volume of 2.0–2.6 BV when acceptable probability was set to 0.80. The verification experimental values were in a good agreement with the predicted values. The design space is reliable and working within it can attain process CQAs criteria with a high probability.
Co-reporter:Xingchu Gong, Huali Chen, Jianyang Pan, Haibin Qu
Separation and Purification Technology 2015 Volume 141() pp:197-206
Publication Date(Web):12 February 2015
DOI:10.1016/j.seppur.2014.11.020
Co-reporter:Binjun Yan;Zhonghua Fang;Lijuan Shen
Phytochemical Analysis 2015 Volume 26( Issue 4) pp:261-268
Publication Date(Web):
DOI:10.1002/pca.2559
Abstract
Introduction
The batch-to-batch quality consistency of herbal drugs has always been an important issue.
Objectives
To propose a methodology for batch-to-batch quality control based on HPLC–MS fingerprints and process knowledgebase.
Methods
The extraction process of Compound E-jiao Oral Liquid was taken as a case study. After establishing the HPLC–MS fingerprint analysis method, the fingerprints of the extract solutions produced under normal and abnormal operation conditions were obtained. Multivariate statistical models were built for fault detection and a discriminant analysis model was built using the probabilistic discriminant partial-least-squares method for fault diagnosis.
Results
Based on multivariate statistical analysis, process knowledge was acquired and the cause–effect relationship between process deviations and quality defects was revealed. The quality defects were detected successfully by multivariate statistical control charts and the type of process deviations were diagnosed correctly by discriminant analysis.
Conclusion
This work has demonstrated the benefits of combining HPLC–MS fingerprints, process knowledge and multivariate analysis for the quality control of herbal drugs. Copyright © 2015 John Wiley & Sons, Ltd.
Co-reporter:Binjun Yan and Haibin Qu
Analytical Methods 2015 vol. 7(Issue 11) pp:4616-4620
Publication Date(Web):24 Apr 2015
DOI:10.1039/C5AY00337G
In process development, the design of experiments (DoE) approach has been widely used for screening the key influential factors and obtaining optimal operating conditions. However, measuring the quality attributes of many products produced in the DoE is time and cost intensive. Therefore, an innovative method using near infrared spectroscopy (NIRS) for rapid screening of CPPs is proposed in this work, taking the ethanol precipitation process of Danhong Injection as a case study. In this work, seven process parameters were studied with a fractional factorial DoE. The supernatants produced were analyzed by NIRS. The spectra were preprocessed and then decomposed by principal component analysis into a few scores and loadings. The scores were taken as the response variables in analysis of variance (ANOVA) to identify the CPPs. The results showed that water content in the concentrate (p < 0.0001), ethanol concentration (p < 0.0001) and ethanol consumption (p < 0.0001) were the three CPPs. To validate the proposed method, the intermediates were analyzed by HPLC. The concentrations of two representative compounds were taken as the response variables in ANOVA and the same three CPPs were identified. The proposed method was successfully applied and the advantages of integrating spectroscopic techniques into screening DoE were demonstrated.
Co-reporter:Wenlong Li, Haifan Han, Lu Zhang, Yan Zhang, Haibin Qu
Sensors and Actuators B: Chemical 2015 211() pp: 131-137
Publication Date(Web):
DOI:10.1016/j.snb.2015.01.073
Co-reporter:Shanshan Zeng, Lu Wang, Teng Chen, Haibin Qu
Analytica Chimica Acta 2014 Volume 811() pp:43-50
Publication Date(Web):6 February 2014
DOI:10.1016/j.aca.2013.12.014
A surface flowing mode sample holder was designed as an alternative sampling strategy for direct analysis in real time mass spectrometry (DART-MS). With the sample holder, the on-line coupling of macroporous resin column chromatography with DART-MS was explored and the new system was employed to monitor the column chromatography elution process of Panax notoginseng. The effluent from macroporous resin column was first diluted and mixed with a derivatization reagent on-line, and the mixture was then directly transferred into the ionization region of DART-MS by the sample holder. Notoginsenosides were methylated and ionized in a metastable helium gas stream, and was introduced into MS for detection. The on-line system showed reasonable repeatability with a relative standard deviation of 12.3% for the peak area. Three notoginsenosides, i.e. notoginsenoside R1, ginsenoside Rb1 and ginsenoside Rg1, were simultaneously determined during the eluting process. The alteration of the chemical composition in the effluent was accurately identified in 9 min, agreeing well with the off-line analysis. The presented technique is more convenient compared to the traditional UPLC method. These results suggest that the surface flowing mode DART-MS has a good potential for the on-line process monitoring in the pharmaceutical industry.
Co-reporter:Binjun Yan, Teng Chen, Zhilin Xu, Haibin Qu
Journal of Pharmaceutical and Biomedical Analysis 2014 Volume 94() pp:106-110
Publication Date(Web):June 2014
DOI:10.1016/j.jpba.2014.01.033
•A method is proposed for rapid process development, which integrates PAT into DoE.•The method is applied in the case study of chromatographic loading process.•DART-MS is used as a PAT tool for fast obtaining the breakthrough curves.•The breakthrough curves obtained by DART-MS and HPLC are in accordance.•Impacts of process parameters on adsorption is obtained rapidly using the method.The concept of quality by design (QbD) is widely applied in the process development of pharmaceuticals. However, the additional cost and time have caused some resistance about QbD implementation. To show a possible solution, this work proposed a rapid process development method, which used direct analysis in real time mass spectrometry (DART-MS) as a process analytical technology (PAT) tool for studying the chromatographic process of Ginkgo biloba L., as an example. The breakthrough curves were fast determined by DART-MS at-line. A high correlation coefficient of 0.9520 was found between the concentrations of ginkgolide A determined by DART-MS and HPLC. Based on the PAT tool, the impacts of process parameters on the adsorption capacity were discovered rapidly, which showed a decreased adsorption capacity with the increase of the flow rate. This work has shown the feasibility and advantages of integrating PAT into QbD implementation for rapid process development.
Co-reporter:Xingchu Gong, Yao Li, Zhengtai Guo, Haibin Qu
Separation and Purification Technology 2014 Volume 132() pp:126-137
Publication Date(Web):20 August 2014
DOI:10.1016/j.seppur.2014.05.014
•Risk assessment is applied to obtain the CQAs of ethanol precipitation process.•Noise parameter influences are minimized by the control of adjustable parameters.•Design space based on probability is calculated using a Monte Carlo method.To provide a new method to develop a design space to improve the robustness of drug manufacturing processes based on the control of noise parameter influences, the ethanol precipitation process of Danhong injection was investigated as a sample. Water content in the concentrated extract (WCCE), the concentration of ethanol (CEA), and the amount of ethanol added (AEA) are three adjustable parameters. The effects of refrigeration temperature (RT) was investigated on three levels for simulating its fluctuations. The models between parameters and process critical quality attributes (CQAs) were obtained using a simplified central composite design with determination coefficients more than 0.84. The decrease of RT led to lower active ingredient recoveries and higher DMR. The increase of CEA and the decrease of WCCE caused more precipitation. The decrease of CEA or AEA resulted in higher active ingredient recoveries. The design space was calculated using an exhaustive search-Monte Carlo method and normal operation ranges were also obtained. The results of verification experiments agreed well with prediction results. The proposed method can be used to develop a design space applicable in a larger scale manufacturing process with the negative effects caused by the fluctuations of noise parameters controlled.
Co-reporter:Lu Wang, Shanshan Zeng, Teng Chen, Haibin Qu
Journal of Pharmaceutical and Biomedical Analysis 2014 Volume 91() pp:202-209
Publication Date(Web):25 March 2014
DOI:10.1016/j.jpba.2013.12.034
•DART-MS was proposed as a PAT tool for real-time monitoring of percolation process.•MPLS model was established to detect and diagnose the batch variations.•Process faults were explained by variable contributions of effective compositions.•DART-MS was proven to be a potential PAT tool for samples in complex matrices.A promising process analytical technology (PAT) tool has been introduced for batch processes monitoring. Direct analysis in real time mass spectrometry (DART-MS), a means of rapid fingerprint analysis, was applied to a percolation process with multi-constituent substances for an anti-cancer botanical preparation. Fifteen batches were carried out, including ten normal operations and five abnormal batches with artificial variations. The obtained multivariate data were analyzed by a multi-way partial least squares (MPLS) model. Control trajectories were derived from eight normal batches, and the qualification was tested by R2 and Q2. Accuracy and diagnosis capability of the batch model were then validated by the remaining batches. Assisted with high performance liquid chromatography (HPLC) determination, process faults were explained by corresponding variable contributions. Furthermore, a batch level model was developed to compare and assess the model performance. The present study has demonstrated that DART-MS is very promising in process monitoring in botanical manufacturing. Compared with general PAT tools, DART-MS offers a particular account on effective compositions and can be potentially used to improve batch quality and process consistency of samples in complex matrices.
Co-reporter:Binjun Yan;Yao Li;Zhengtai Guo
Phytochemical Analysis 2014 Volume 25( Issue 1) pp:59-65
Publication Date(Web):
DOI:10.1002/pca.2463
ABSTRACT
Introduction
The concept of quality by design (QbD) has been widely accepted and applied in the pharmaceutical manufacturing industry. There are still two key issues to be addressed in the implementation of QbD for herbal drugs. The first issue is the quality variation of herbal raw materials and the second issue is the difficulty in defining the acceptable ranges of critical quality attributes (CQAs).
Objective
To propose a feedforward control strategy and a method for defining the acceptable ranges of CQAs for the two issues.
Methods
In the case study of the ethanol precipitation process of Danshen (Radix Salvia miltiorrhiza) injection, regression models linking input material attributes and process parameters to CQAs were built first and an optimisation model for calculating the best process parameters according to the input materials was established. Then, the feasible material space was defined and the acceptable ranges of CQAs for the previous process were determined.
Results
In the case study, satisfactory regression models were built with cross-validated regression coefficients (Q2) all above 91 %. The feedforward control strategy was applied successfully to compensate the quality variation of the input materials, which was able to control the CQAs in the 90–110 % ranges of the desired values. In addition, the feasible material space for the ethanol precipitation process was built successfully, which showed the acceptable ranges of the CQAs for the concentration process.
Conclusion
The proposed methodology can help to promote the implementation of QbD for herbal drugs. Copyright © 2013 John Wiley & Sons, Ltd.
Co-reporter:Haoshu Xiong, Lawrence X. Yu and Haibin Qu
Analytical Methods 2014 vol. 6(Issue 2) pp:476-481
Publication Date(Web):08 Nov 2013
DOI:10.1039/C3AY41728J
The batch-to-batch quality consistency needs to be controlled to ensure the efficacy and safety of botanical drug products. Chromatographic fingerprinting is a powerful tool for characterizing complex chemical systems such as botanical drugs. This paper presented the combined use of a proposed weighting algorithm and multivariate statistical analysis on fingerprint data to achieve quality consistency evaluation of botanical drug products. A set of fingerprint data following multivariate normal distribution was simulated based on the real fingerprint data of a botanical drug product, Danshen injection. The weight of each peak was set based on its batch-to-batch peak variation. A principal component analysis (PCA) model was established, and the Hotelling T2 and DModX statistics were applied to evaluate quality consistency. The effect of weighting on the monitoring capability of the two statistics was evaluated through monitoring simulated peak area variations. The results showed that both the two statistics were more sensitive to the characteristic peaks with smaller batch-to-batch peak variations. Hence the peaks with larger variability will be permitted to have a wider tolerance range of variation, while a more narrow range of variation was seen for the peaks with smaller variability among batches. Peak weighting combined with multivariate statistical analysis has overcome some drawbacks of the fingerprint similarity analysis method, and is worthy of application and recommendation for the quality consistency evaluation of botanical drug products.
Co-reporter:Lu Wang;Teng Chen;Shanshan Zeng
Journal of The American Society for Mass Spectrometry 2014 Volume 25( Issue 2) pp:278-285
Publication Date(Web):2014 February
DOI:10.1007/s13361-013-0779-6
A mass spectrometry method has been developed using the Quality by Design (QbD) principle. Direct analysis in real time mass spectrometry (DART-MS) was adopted to analyze a pharmaceutical preparation. A fishbone diagram for DART-MS and the Plackett-Burman design were utilized to evaluate the impact of a number of factors on the method performance. Multivariate regression and Pareto ranking analysis indicated that the temperature, determined distance, and sampler speed were statistically significant (P < 0.05). Furthermore, the Box-Behnken design combined with response surface analysis was then employed to study the relationships between these three factors and the quality of the DART-MS analysis. The analytical design space of DART-MS was thus constructed and its robustness was validated. In this presented approach, method performance was mathematically described as a composite desirability function of the critical quality attributes (CQAs). Two terms of method validation, including analytical repeatability and method robustness, were carried out at an operating work point. Finally, the validated method was successfully applied to the pharmaceutical quality assurance in different manufacturing batches. These results revealed that the QbD concept was practical in DART-MS method development. Meanwhile, the determined quality was controlled by the analytical design space. This presented strategy provided a tutorial to the development of a robust QbD-compliant mass spectrometry method for industrial quality control.
Co-reporter:Binjun Yan
Journal of Separation Science 2013 Volume 36( Issue 7) pp:1231-1237
Publication Date(Web):
DOI:10.1002/jssc.201200879
Chromatography using polyamide column is one of the most critical purification operations that affect the safety and efficacy of traditional Chinese medicine (TCM) products. To ensure successful operation and reduce time and solvent consumption, UV spectroscopy combined with multivariate data analysis as an online analytical tool was developed for monitoring the polyamide column chromatography of the TCM Danshen. The process trajectories were established by principal component analysis of the UV spectra and used to determine the endpoint of the washing stage and investigate the impacts of the process conditions. The online analysis method developed determined the concentration of salvianolic acid B (an important compound in Danshen) in the effluent rapidly and precisely with a coefficient of determination of 0.9963 and helped to collect salvianolic acid B quantitatively for determining the endpoint of elution. The methodology proposed is an effective approach applicable in guiding successful operations in the chromatographic separation.
Co-reporter:Cheng Jiang, Xingchu Gong, Haibin Qu
Separation and Purification Technology 2013 Volume 116() pp:287-293
Publication Date(Web):15 September 2013
DOI:10.1016/j.seppur.2013.05.049
•The adsorption efficiencies at the end of the process were predicted early-on.•Process parameters were adjusted according to the raw materials variation.•The strategy can lead the process towards the target adsorption efficiencies.The manufacturing process efficiencies and the products quality of herbal medicine often suffer from high variability with the variability of the raw materials. This paper presents a methodology for adjusting process parameters according to the raw materials variation for acceptable adsorption efficiencies during HM column chromatography process. The methodology was illustrated by an example of saponins adsorption process, which is a critical unit operation in macroporous resin column chromatography during Panax notoginseng injection manufacturing process. The impact of total saponins concentration in loading solution and adsorption time on adsorption efficiencies was mapped. The specification region of raw material was obtained and the adsorption efficiencies at the end of the adsorption process were predicted early-on. When the predicted adsorption efficiencies did not meet the target values, the control method proposed the use of an adjusted process parameter leading the adsorption process towards the target adsorption efficiencies at the end of the adsorption process. The results in this work facilitated the enhanced understanding of the relationships between raw material attributes, process parameters and saponins adsorption efficiencies. This case study demonstrated that it is possible to employ different process parameters to accommodate raw materials variation for acceptable process efficiencies.Graphical abstractThe adsorption efficiencies were predicted according to the raw materials variation and the process parameters were adjusted early-on, hence guiding the adsorption efficiencies towards the target values.
Co-reporter:Jianyang Pan, Xingchu Gong, Haibin Qu
Journal of Pharmaceutical and Biomedical Analysis 2013 Volume 85() pp:28-32
Publication Date(Web):November 2013
DOI:10.1016/j.jpba.2013.06.020
•Q-NMR method to determine Sal B as well as its degradation products is described.•The method is applied to monitor the hydrolysis of Sal B in low oxygen condition.•The concentration results are fitted to a kinetic model to obtain rate constants.•Q-NMR method is proved to be suitable and effective for degradation study.This work presents an exploratory study for monitoring the hydrolytic process of salvianolic acid B (Sal B) in low oxygen condition using a simple quantitative 1H NMR (Q-NMR) method. The quantity of the compounds was calculated by the relative ratio of the integral values of the target peak for each compound to the known amount of the internal standard trimethylsilyl propionic acid (TSP). Kinetic runs have been carried out on different initial concentrations of Sal B (5.00, 10.0, 20.0 mg/mL) and temperatures of 70, 80, 90 °C. The effect of these two factors during the transformation process of Sal B was investigated. The hydrolysis followed pseudo-first-order kinetics and the apparent degradation kinetic constant at 80 °C decreased when concentration of Sal B increased. Under the given conditions, the rate constant of overall hydrolysis as a function of temperature obeyed the Arrhenius equation. Six degradation products were identified by NMR and mass spectrometric analysis. Four of these degradation products, i.e. danshensu (DSS), protocatechuic aldehyde (PRO), salvianolic acid D (Sal D) and lithospermic acid (LA) were further identified by comparing the retention times with standard compounds. The advantage of this Q-NMR method was that no reference compounds were required for calibration curves, the quantification could be directly realized on hydrolyzed samples. It was proved to be simple, convenient and accurate for hydrolytic kinetic study of Sal B.
Co-reporter:Shanshan Zeng, Teng Chen, Lu Wang, Haibin Qu
Journal of Pharmaceutical and Biomedical Analysis 2013 Volume 76() pp:87-95
Publication Date(Web):25 March 2013
DOI:10.1016/j.jpba.2012.12.014
Batch-to-batch variability of traditional Chinese medicine (TCM) has already heavily limited its industrial development. By utilizing direct analysis in real time mass spectrometry (DART-MS) and multivariate statistical analysis, the present study introduced a novel and rapid methodology for TCM manufacturing process monitoring. Danshen alkaline precipitation was employed as an example operating unit to demonstrate the effectiveness of this new technique. A total of 15 batches run under normal operating conditions were used to develop a reference principal component analysis model and then enabled the establishment of multivariate control charts. Hotteling T2 and DModX charts were applied to examine batch-to-batch reproducibility of 12 test batches. Artificial variations including starting material change and process fault were identified, which was in a good agreement with conventional analysis result. Further understanding of the deviating process behavior was achieved by investigating the contribution plot of abnormal batches. The results showed that DART-MS, in conjunction with multivariate analysis, provided valuable information on model process and gave us a new perspective for TCM manufacturing process monitoring.Graphical abstractHighlights► DART-MS was used to monitor the batch-to-batch consistency of TCM manufacture. ► DART-MS data were processed by PCA and then statistical process control method. ► Control limits were established to detect batch-to-batch consistency or variation.
Co-reporter:Wenlong Li, Zhiwei Cheng, Yuefei Wang, Haibin Qu
Journal of Pharmaceutical and Biomedical Analysis 2013 Volume 72() pp:33-39
Publication Date(Web):18 January 2013
DOI:10.1016/j.jpba.2012.09.012
A set of qualitative and quantitative methods based on near infrared (NIR) spectroscopy was established for the geographical origin identification, quantitative determination of active compounds, and fingerprint analysis of Lonicerae Japonicae Flos. The spectra of 140 samples from different origins were collected with two NIR instruments from different manufacturers (Thermo Scientific and Buchi). A Soft Independent Modeling of Class Analogy model was established for the identification of Lonicerae Japonicae Flos from the genuine producing area. Using the established discriminant analysis model, 22 samples from Henan province were predicted with 100% rate of accuracy, while the 68 samples from other producing areas were predicted with 9 samples incorrectly judged. Futhermore, partial least square regression method was used for developing the quantitative calibration models with the reference values determined with a validated HPLC–UV method. The RMSEP values of external validation are 0.169%, 0.048%, 0.172%, 0.007%, 0.203%, and 0.066% for NCA, CA, CfA, 3,4-DCA, 3,5-DCA, and 4,5-DCA, respectively, which indicated that the established models possess satisfactory predictive abilities. In addition, the models established on the primary instrument can also be transferred to the secondary instrument using direct standardization algorithm, which enlarged the application scope of the established models. Since the NIR spectra can reflect the comprehensive quality information of Lonicerae Japonicae Flos, a fingerprint analysis method was finally proposed for the quality consistency check of raw materials. The proposed methods are rapid and effective, and possess good portability, which is helpful to the quality control of Lonicerae Japonicae Flos.Highlights► A SIMCA model was established for the identification of Lonicerae Japonicae Flos. ► PLS calibration models were established for the 6 organic acids. ► The established models were transferred with DS method between two NIR instruments. ► A fingerprint method was proposed for the consistency check of TCM materials.
Co-reporter:Xingchu Gong, Shanshan Wang, Yao Li, Haibin Qu
Separation and Purification Technology 2013 Volume 107() pp:273-280
Publication Date(Web):2 April 2013
DOI:10.1016/j.seppur.2013.01.029
Ethanol precipitation is a widely applied separation technology in the production of botanical medicines, but the research on this technology is few. In this work, ethanol precipitation is used to purify the water extract of Danshen (Salvia miltiorrhiza Bge.) and Chuanxiong (Ligusticum chuanxiong Hort.) as a sample to describe its separation characteristics and mechanism. The effects of refrigeration temperature, ethanol addition, and supernatant pH value were investigated. Total saccharide removal and dry matter removal increased as refrigeration temperature decreased or ethanol addition increased. Danshensu (DSS) recovery and salvianolic acid B (SaB) recovery increased as supernatant pH value decreased or ethanol addition decreased. The purity of phenolic compounds increased after ethanol precipitation. The losses of caffeic acid (CA) and ferulic acid (FA) in ethanol precipitation were caused by chemical transformation. The losses of DSS and SaB were both caused by chemical transformation and precipitation. By using a simple model, the pKa values of DSS and SaB in supernatant can be calibrated, which were 3.63 and 3.56, respectively. The solubilities of DSS salt and SaB salt can also be calibrated. Most of DSS and SaB existed in supernatant in their ionic forms. The results of this work will contribute to the implementation of Quality by design (QbD) concept in the manufacture of botanical medicines.Highlights► Separation characteristics of ethanol precipitation were investigated. ► The mechanism of active constituent loss was investigated. ► A novel model based on dissociation and dissolution equilibriums was established.
Co-reporter:Hongxia Huang and Haibin Qu
Analytical Methods 2013 vol. 5(Issue 2) pp:474-482
Publication Date(Web):12 Nov 2012
DOI:10.1039/C2AY25925G
Very few efforts have been directed toward interpreting the differences between chromatographic and spectroscopic fingerprints for the purpose of quality control, although similarity analysis based on fingerprints is commonly applied to quality consistency evaluation of herbal medicines (HM). In the current study, comparative evaluation of high-performance liquid chromatography (HPLC), ultraviolet (UV), and near-infrared (NIR) fingerprint techniques combined with chemometric methods has been conducted to control the quality of Chinese herbal injections. A set of Danshen injections (DSI) are chosen as an example of the relevance to contemporary HM. Similarity analysis by principal component analysis, identification using linear discriminant analysis and k nearest neighbor classifiers, and control charts based on Hotelling's T2 and DModX statistics are employed to evaluate the quality consistency of the DSI samples from three different manufacturers. The results in this study demonstrate that the UV spectroscopy technique combined with chemometric methods is useful for the identity and consistency evaluation of DSI. Such an approach is believed to be equally applicable to other HM.
Co-reporter:Cheng Jiang, Yin Liu and Haibin Qu
Analytical Methods 2013 vol. 5(Issue 17) pp:4467-4475
Publication Date(Web):28 May 2013
DOI:10.1039/C3AY26540D
A data fusion method based on near infrared (NIR) spectra and ultraviolet (UV) spectra for simultaneous determination of six ginsenosides and four saccharides in Chinese herbal injection (CHI) was developed. Two data fusion strategies (low-level data fusion and mid-level data fusion) combined with partial least squares (PLS) regression and uninformative variable elimination by PLS (UVEPLS) regression were implemented, respectively. Compared with the models established by independent NIR or UV spectra, there was a significant improvement provided by two data fusion strategies, which benefited from the synergistic effect of complementary information obtained from near infrared spectroscopy (NIRS) and ultraviolet spectroscopy (UVS). The results in this work showed data fusion of NIR and UV spectra combined with a regression algorithm could be a promising strategy to determine the ginsenosides and saccharides in CHI rapidly and simultaneously.
Co-reporter:Haoshu Xiong, Xueyong Qi and Haibin Qu
Analytical Methods 2013 vol. 5(Issue 2) pp:465-473
Publication Date(Web):14 Nov 2012
DOI:10.1039/C2AY25705J
In traditional Chinese medicinal production, a high degree of batch-to-batch reproducibility is required to achieve successful batches that meet the quality standard of traditional Chinese medicinal preparations (TCMPs). In this paper, multivariate statistical process monitoring (MSPM) based on chromatographic fingerprinting has been introduced to evaluate the batch-to-batch reproducibility of TCMPs. A commonly used TCMP product, Sheng-Mai-Yin (SMY) oral liquid, is selected as a typical example to demonstrate the feasibility of this approach. A number of batches are prepared through normal operation procedures to simulate the common-cause variations induced by preparation days, herb materials, and operators. Another number of abnormal batches are designed to simulate different types of deviations, including the changes of herb material quality attributes and abnormal operation conditions. The high-performance liquid chromatographic fingerprinting is used to construct the integrative pattern of SMY products. A principle component analysis model is established of the fingerprint data of the normal batches. Multivariate (Hotelling T2 and DModX) control charts are successfully applied to monitor the abnormal batches. As an effective multivariate analysis method in this study, MSPM based on chromatographic fingerprinting promises great applications in batch monitoring and evaluation for the production of TCMPs.
Co-reporter:Wenlong Li, Zhiwei Cheng, Yuefei Wang, Haibin Qu
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy 2013 Volume 101() pp:1-7
Publication Date(Web):15 January 2013
DOI:10.1016/j.saa.2012.09.044
In this paper we describe the strategy used in the development and validation of a near infrared spectroscopy method for the rapid determination of baicalin, chlorogenic acid, ursodeoxycholic acid (UDCA), chenodeoxycholic acid (CDCA), and the total solid contents (TSCs) in the Tanreqing injection. To increase the representativeness of calibration sample set, a concentrating–diluting method was adopted to artificially prepare samples. Partial least square regression (PLSR) was used to establish calibration models, with which the five quality indicators can be determined with satisfied accuracy and repeatability. In addition, the slope/bias (S/B) method was used for the models transfer between two different types of NIR instruments from the same manufacturer, which is contributing to enlarge the application range of the established models. With the presented method, a great deal of time, effort and money can be saved when large amounts of Tanreqing injection samples need to be analyzed in a relatively short period of time, which is of great significance to the traditional Chinese medicine (TCM) industries.Graphical abstractThe figure is the near infrared spectra of Tanreqing injection samples collected with two NIR instruments. In this article, the PLS calibration models were established with the spectra data and the references values, and the S/B method was used for the models transfer between the two different types of NIR instruments from the same manufacturer.Highlights► Firstly reported the application of NIR spectroscopy in the quality control of CMI. ► Concentrating–diluting method increases the representativeness of calibration set. ► S/B method was used for the models transfer between two NIR instruments.
Co-reporter:Bin-jun Yan;Hai-bin Qu
Journal of Zhejiang University-SCIENCE B 2013 Volume 14( Issue 11) pp:1041-1048
Publication Date(Web):2013 November
DOI:10.1631/jzus.B1300059
The efficacy of traditional Chinese medicine (TCM) is based on the combined effects of its constituents. Variation in chemical composition between batches of TCM has always been the deterring factor in achieving consistency in efficacy. The batch mixing process can significantly reduce the batch-to-batch quality variation in TCM extracts by mixing them in a well-designed proportion. However, reducing the quality variation without sacrificing too much of the production efficiency is one of the challenges. Accordingly, an innovative and practical batch mixing method aimed at providing acceptable efficiency for industrial production of TCM products is proposed in this work, which uses a minimum number of batches of extracts to meet the content limits. The important factors affecting the utilization ratio of the extracts (URE) were studied by simulations. The results have shown that URE was affected by the correlation between the contents of constituents, and URE decreased with the increase in the number of targets and the relative standard deviations of the contents. URE could be increased by increasing the number of storage tanks. The results have provided a reference for designing the batch mixing process. The proposed method has possible application value in reducing the quality variation in TCM and providing acceptable production efficiency simultaneously.
Co-reporter:Shanshan Zeng, Lu Wang, Teng Chen, Yuefei Wang, Huanbiao Mo, Haibin Qu
Analytica Chimica Acta 2012 Volume 733() pp:38-47
Publication Date(Web):6 July 2012
DOI:10.1016/j.aca.2012.04.025
The paper presents a novel strategy to identify analytical markers of traditional Chinese medicine preparation (TCMP) rapidly via direct analysis in real time mass spectrometry (DART-MS). A commonly used TCMP, Danshen injection, was employed as a model. The optimal analysis conditions were achieved by measuring the contribution of various experimental parameters to the mass spectra. Salvianolic acids and saccharides were simultaneously determined within a single 1-min DART-MS run. Furthermore, spectra of Danshen injections supplied by five manufacturers were processed with principal component analysis (PCA). Obvious clustering was observed in the PCA score plot, and candidate markers were recognized from the contribution plots of PCA. The suitability of potential markers was then confirmed by contrasting with the results of traditional analysis methods. Using this strategy, fructose, glucose, sucrose, protocatechuic aldehyde and salvianolic acid A were rapidly identified as the markers of Danshen injections. The combination of DART-MS with PCA provides a reliable approach to the identification of analytical markers for quality control of TCMP.Graphical abstractHighlights► DART-MS combined with PCA was used to rapidly identify markers of herbal preparation. ► Salvianolic acids and saccharides were simultaneously determined with DART-MS. ► DART-MS spectra obtained from batches of Danshen injections were processed using PCA. ► Candidate markers of Danshen injection were recognized from the contribution plots.
Co-reporter:Xintian Zheng, Xingchu Gong, Qin Li, and Haibin Qu
Industrial & Engineering Chemistry Research 2012 Volume 51(Issue 8) pp:3238-3245
Publication Date(Web):January 4, 2012
DOI:10.1021/ie201536y
This work presents an exploratory study of monitoring the transformation process of salvianolic acid A (SAA) using an online UV spectroscopic analysis system. A chemometrics approach, based on multivariate curve resolution of spectrophotometric matrix, was applied to resolve the concentration and spectra profiles of reactant species and to evaluate the kinetic profile. Kinetic runs have been developed at temperatures ranging from 25 to 90 °C and pH values ranging from 2.5 to 10 in order to investigate the effects of these two variables during the transformation process of SAA. The degradation reaction of SAA was considered as first-order and the degradation kinetic constant of SAA increases when temperature increases. It was also found that SAA transforms rapidly when pH is higher than 7, but remains stable when pH is lower than 6.5. Two transformation products were auxiliarily identified by direct mass spectrometric analysis using Mass Work software. Our results suggest that the manufacturing process of Chinese medicine preparations with SAA as the main bioactive compound should not be operated at high temperature and high pH.
Co-reporter:Wenlong Li, Yuefei Wang, Haibin Qu
Vibrational Spectroscopy 2012 Volume 62() pp:159-164
Publication Date(Web):September 2012
DOI:10.1016/j.vibspec.2012.07.005
There is a lack of methods to analyze large numbers of traditional Chinese medicine (TCM) samples quickly and efficiently. Here we present a near infrared (NIR) spectroscopy-based method for the rapid analysis of Honeysuckle extracts. NIR spectra of 124 Honeysuckle extract samples produced within a four-year period were collected in the diffuse reflection mode and pretreated with multiplicative scatter correction (MSC), smoothing and derivative. Using partial least squares regression (PLSR), including PLS1 and PLS2, we established and validated the calibration models of six organic acids. Our results showed that both accuracy and precision of the NIR spectroscopy-based method meet the requirements of a traditional Chinese medicine (TCM) factory. This new method has the potential to save time, efforts and cost associated with the analysis of large quantities of unknown samples and will be particularly applicable to TCM factories for cost reduction.
Co-reporter:Zheng Xintian ;Qu Haibin
Phytochemical Analysis 2012 Volume 23( Issue 2) pp:103-109
Publication Date(Web):
DOI:10.1002/pca.1330
ABSTRACT
Introduction
Chinese herbal medicines contain complex ingredients that are unstable during the manufacturing process. Current off-line methods are usually time-consuming and inaccurate.
Objective
The aim of this study was to develop a continuous-flow-based on-line spectroscopic system for monitoring the degradation of unstable compounds in Chinese herbal medicines.
Methodology
An on-line spectroscopic analysis system in the evaluation of the degradation of unstable compounds was implemented, using salvianolic acid B from Danshen (Radix Salviae Miltiorrhizae) as a model compound. Resolution of the mixture spectra obtained during the reaction was performed with multivariate curve resolution (MCR), and the pure spectra and kinetic profiles of reactant species were reconstructed.
Results
The degradation process of salvianolic acid B is probably a consecutive two-step reaction of the form A B C, where A is salvianolic acid B, and B and C are the intermediate and final products, respectively. The intermediate and final products were suggested to be a mixture of lithospermic acid and danshensu [3-(3, 4-dihydroxyphenyl) lactic acid], and a mixture of danshensu and salvianolic acid A, respectively.
Conclusion
The findings suggested that the combined use of on-line spectroscopic analysis and MCR might be a cheap, readily available, sensitive tool to monitor the transformation of unstable components of Chinese herbal medicines. Copyright © 2011 John Wiley & Sons, Ltd.
Co-reporter:Xingchu Gong, Chuan Wang, Lei Zhang, and Haibin Qu
Journal of Chemical & Engineering Data 2012 Volume 57(Issue 11) pp:3264-3269
Publication Date(Web):October 24, 2012
DOI:10.1021/je300885g
The solubilities of (2R,3S,4R)-2,3,4,5-tetrahydroxypentanal (xylose), (2R,3R,4R,5R)-2,3,5,6-tetrahydroxy-4-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyhexanal hydrate (maltose monohydrate), (2R,3S,4S,5R,6R)-2-(hydroxymethyl)-6-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxane-3,4,5-triol dihydrate (trehalose dihydrate), and (3S,4S,5S,6R)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol (mannose) in the mixtures of ethanol and water from (278.2 to 298.2) K were determined. The solubilities of all the four saccharides in ethanol–water mixtures increased as equilibrium temperature increased. The solubilities of trehalose dihydrate, xylose, and mannose decreased as ethanol mass fraction in the mixed solvent increased. Maltose monohydrate solubility decreased when ethanol mass fraction in the mixed solvent was less than 0.9. The solubilities of xylose and mannose were predicted with A-UNIFAC, and the average relative deviations (ARD) values were less than 22 %. The solubilities of maltose monohydrate and trehalose dihydrate were calculated with the modified UNIQUAC model. New interaction parameters were calibrated. The ARD values for trehalose dihydrate solubility and maltose monohydrate solubility are 28.6 % and 17.9 %, respectively.
Co-reporter:Haoshu Xiong, Xingchu Gong, Haibin Qu
Journal of Pharmaceutical and Biomedical Analysis 2012 70() pp: 178-187
Publication Date(Web):
DOI:10.1016/j.jpba.2012.06.028
Co-reporter:Lei Zhang, Xingchu Gong, Yuefei Wang, and Haibin Qu
Journal of Chemical & Engineering Data 2012 Volume 57(Issue 7) pp:2018-2022
Publication Date(Web):June 13, 2012
DOI:10.1021/je300323g
3,4-Dihydroxybenzaldehyde (protocatechuic aldehyde), (E)-3-(3,4-dihydroxyphenyl)prop-2-enoic acid (caffeic acid), (2S,3R,4S,5R,6R)-6-(hydroxymethyl)oxane-2,3,4,5-tetrol (d-galactose), and (3R,4S,5R,6R)-2-[[(2R,3S,4S,5R)-6-[(2S,3S,4S,5R)-3,4-dihydroxy-2,5-bis(hydroxymethyl)oxolan-2-yl]oxy-3,4,5-trihydroxyoxan-2-yl]methoxy]-6-(hydroxymethyl)oxane-3,4,5-triol (d-raffinose) are substances contained in danshen. In this study, the solubilities of protocatechuic aldehyde, caffeic acid, d-galactose, and d-raffinose pentahydrate in the mixtures of ethanol and water from 273.2 K to 303.2 K were determined. The solubilities of protocatechuic aldehyde and caffeic acid in ethanol–water solutions are significantly higher than those in pure water. The solubilities of d-galactose and d-raffinose pentahydrate decrease as ethanol mass fraction increases. The solubilities of the four compounds increase as equilibrium temperature increases. Prediction values of d-galactose calculated using universal functional activity coefficient (UNIFAC) models agreed well with experimental data.
Co-reporter:Hongxia Huang, Haibin Qu
Analytica Chimica Acta 2011 Volume 707(1–2) pp:47-56
Publication Date(Web):30 November 2011
DOI:10.1016/j.aca.2011.09.031
Alcohol precipitation is a critical unit operation during the manufacture of Chinese herbal injections. To facilitate enhanced process understanding and develop control strategy, the use of near-infrared spectroscopy (NIRS) combined with multivariate statistical process control (MSPC) methodology was investigated for in-line monitoring of alcohol precipitation. The effectiveness of the proposed approach was evaluated through an experimental campaign. Six batches were run under normal operating conditions to study batch-to-batch variation or batch reproducibility and establish MSPC control limits, while artificial process variations were purposefully introduced into the four test batches to assess the capability of the model for real-time fault detection. Several MSPC tools were compared and assessed. NIRS, in conjunction with MSPC, has proven to be a feasible process analytical technology (PAT) tool for monitoring batch evolution and potentially facilitating model-based advanced process control of the alcohol precipitation during the manufacture of Chinese herbal injections.Graphical abstractBatch score control charts (t1) based on six NOC batches with control limits (±3 SD) dyed solid black line, and average trace marked by dotted black line: (a) batch 7, (b) batch 8, (c) batch 9, (d) batch 10.Highlights► NIRS combined with MSPC was proposed for in-line monitoring of alcohol precipitation. ► MSPC control limits were established to detect and diagnose batch-to-batch variation. ► The method has proven to be a feasible PAT tool for monitoring batch evolution.
Co-reporter:Xingchu Gong, Shanshan Wang, and Haibin Qu
Industrial & Engineering Chemistry Research 2011 Volume 50(Issue 12) pp:7542-7548
Publication Date(Web):May 4, 2011
DOI:10.1021/ie2004972
A botanical injection is a special drug preparation with extremely high safety requirements. Therefore, many separation technologies, such as ethanol precipitation and liquid–liquid extraction, are applied in the manufacturing process of botanical injections to purify efficacy compounds and remove impurities. In this work, second ethanol precipitation and 1-butanol extraction were compared in the purification of the concentrated supernatant of danshen (the dried root of Salvia miltiorrhiza). These two separation technologies showed satisfactory recovery of phenolic compounds and similar removal of total protein. Liquid–liquid extraction removed more saccharides than second ethanol precipitation. Accordingly, the purity of phenolic compounds increased remarkably after liquid–liquid extraction. According to the characteristics of the two separation technologies, the combination technology of “ethanol precipitation + liquid–liquid extraction” showed more advantages in drug safety and product quality control than the combination technology of “ethanol precipitation + second ethanol precipitation”.
Co-reporter:Wenlong Li, Lihong Xing, Yu Cai, Haibin Qu
Vibrational Spectroscopy 2011 Volume 55(Issue 1) pp:58-64
Publication Date(Web):18 January 2011
DOI:10.1016/j.vibspec.2010.07.004
A rapid near infrared spectroscopy analysis method was developed for the geographical origin discrimination and content determination of Radix scutellariae, a kind of Traditional Chinese Medicine (TCM). 81 R. scutellariae samples from six different origins were analyzed with HPLC–UV as reference method. The NIR spectra were collected in integrating-sphere diffused reflection mode and processed with different spectra pretreated methods. Discriminant analysis (DA) and discriminant partial least squares (DPLS) were applied to classify the geographical origins of those samples, and the latter had a better predictive ability with 100% accuracy after two exceptional samples eliminated from the calibration set. For the quantitative calibration, the samples were divided into calibration set and validation set by Kennard–Stone algorithm. The models of baicalin, wogonoside, baicalein, wogonin were established with partial least squares (PLS) algorithm and the optimal principal component (PC) numbers were selected with Leave-One-Out (LOO) cross-validation. The established models were evaluated with the root mean square error of prediction (RMSEP) and corresponding correlation coefficients. The correlation coefficients of all the four calibration models are above 0.920, and the RMSEPs of baicalin, wogonoside, baicalein and wogonin are 0.752%, 0.094%, 0.418% and 0.139%, respectively. This research indicated that the NIR diffuse reflection spectroscopy could be used for the rapid analysis of R. scutellariae, which is beneficial to the quality control of this raw material in TCM pharmaceutical factory, and will also help to solve analogous problems.
Co-reporter:Yongyi Wang;Jinzhong Xu
Phytochemical Analysis 2011 Volume 22( Issue 2) pp:166-171
Publication Date(Web):
DOI:10.1002/pca.1263
Abstract
Introduction – Steroidal saponins are the main active constituents in Ophiopogon japonicus Ker-Gawler (Liliaceae). However, because of their high polarity, non-chromophores and low content in plants, steroidal saponins are difficult to be isolated from O. japonicus by conventional phytochemical methods.
Objective – To develop a sensitive and rapid approach towards the structural analysis of steroidal saponins using HPLC/ESI-MSn.
Methodology – The fragmentation behaviors of six known steroidal saponins in negative ESI-MSn were used to deduce their mass spectral fragmentation mechanisms. By using HPLC/ESI-MSn, the important structural information on aglycone types, sugar types and saccharide sequences can be obtained.
Results – According to the HPLC retention behaviour, the molecular structural characteristics provided by multistage mass spectrometry spectra and the literature, a total of 8 steroidal saponins were tentatively identified or characterized in O. japonicus rapidly. Conclusion – This work has shown that HPLC-ESI-MSn may be used as an effective and rapid method for the characterization and identification of steroidal saponins from O. japonicus. Copyright © 2010 John Wiley & Sons, Ltd.
Co-reporter:Shu-fang Wang;Hai-yan Fang;Hai-bin Qu
Journal of Zhejiang University-SCIENCE B 2011 Volume 12( Issue 3) pp:193-200
Publication Date(Web):2011 March
DOI:10.1631/jzus.B1000135
Central composite design (CCD), together with multiple linear regression, was successfully used to optimize the electrophoretic buffer system of micellar electrokinetic capillary chromatography (MEKC) for the determination of albiflorin, paeoniflorin, liquiritin, and glycyrrhizic acid in the traditional Chinese medicine (TCM) prescription, Yangwei granule. Concentrations of sodium deoxycholate (SDC) and borate, and proportions of ammonia, acetonitrile, and methanol were optimized. The total resolutions of peaks between the analytes and their adjacent peaks in real samples were integrated into the evaluation index of separation efficiency. The optimum electrophoretic buffer contained 80 mmol/L SDC, 20 mmol/L borate, 5% (v/v) methanol, 0.5% (v/v) ammonia, and 5% (v/v) acetonitrile. The correlation coefficients (R2) between the peak areas and the corresponding concentrations of analytes were greater than 0.9956. The limits of detection (LODs) (S/N=3) of the analytes were 0.97–4.00 μg/ml. The results indicate the superiority of CCD in optimizing the separation conditions of complex samples such as TCM prescriptions.
Co-reporter:Bin Wu, Lishe Gan and Haibin Qu
Journal of Natural Products 2010 Volume 73(Issue 6) pp:1069-1074
Publication Date(Web):June 2, 2010
DOI:10.1021/np100063q
A 6-eremophilene derivative 2 with an unusual pendant was produced as phytoalexin in the fresh leaves of Chloranthus anhuiensis K. F. Wu in response to abiotic stress elicitation by CuCl2. The phytoalexin was characterized as a sesquiterpene with a (2,6-dimethoxy-4-hydroxy)benzyl moiety pendant. Two new sesquiterpenes, (3R,4S,5R,10S,11S)-3-hydroxy-8-oxo-6-eremophilen-12-oic acid (1) and (3R,4S,5R,6R,8R,10S)-3,6,8-trihydroxy-7(11)-eremophilen-12,8-olide (3), one new sesquiterpene glycoside, anhuienoside A (4), one new caffeoyl phenylethanoid diglycoside with an unusual cyclic structure, anhuienoside B (5), and one new tyramine derivative, N-acetyltyramine 1-O-β-d-glucoside (6), and three known compounds were also isolated. Their structures and relative configurations were established by spectroscopic means. The absolute configurations of 1−3 were defined mainly by comparison of quantum chemical TDDFT calculated and experimental ECD spectra.
Co-reporter:Yongyi Wang;Jinzhong Xu;Lei Zhang
Helvetica Chimica Acta 2010 Volume 93( Issue 5) pp:
Publication Date(Web):
DOI:10.1002/hlca.200900333
Abstract
Three new homoisoflavanones, 1–3, together with a known one, 4, were obtained from the AcOEt extract of the tuberous roots of Ophiopogon japonicus (Liliaceae). They were identified as (3R)-2,3-dihydro-7-hydroxy-5-methoxy-3-(4-methoxybenzyl)-6,8-dimethyl-4H-chromen-4-one (1), (3R)-3-(1,3-benzodioxol-5-ylmethyl)-2,3-dihydro-7-hydroxy-5-methoxy-6,8-dimethyl-4H-chromen-4-one (2), (3R)-3-(1,3-benzodioxol-5-ylmethyl)-2,3-dihydro-7-hydroxy-5-methoxy-6-methyl-4H-chromen-4-one (3), and ophiopogonanone A (4). Their structures were determined on the basis of extensive NMR-spectroscopic and mass-spectrometric analyses. The three new compounds are rare homoisoflavanones which contain a MeO group at C(5). Compounds 1 and 2 showed weak cytotoxicity against the HepG2 (human hepatoma G2), KB (human oral epidermoid carcinoma), and MCF-7 (human breast adenocarcinoma) cell lines in an MTT assay. Compound 3 exhibited weak cytotoxicity against HepG2 and MCF-7, and moderate cytotoxicity against KB cell lines. Compound 4 showed moderate cytotoxicity against HepG2, KB, and MCF-7 cell lines.
Co-reporter:Wenlong Li, Haibin Qu
Journal of Pharmaceutical and Biomedical Analysis 2010 52(4) pp: 425-431
Publication Date(Web):
DOI:10.1016/j.jpba.2010.01.009
Co-reporter:Wenlong Li, Lihong Xing, Limin Fang, Jue Wang, Haibin Qu
Journal of Pharmaceutical and Biomedical Analysis 2010 53(3) pp: 350-358
Publication Date(Web):
DOI:10.1016/j.jpba.2010.04.011
Co-reporter:Hong Yao, Bin Wu, Haibin Qu, Yiyu Cheng
Analytica Chimica Acta 2009 Volume 633(Issue 1) pp:76-80
Publication Date(Web):2 February 2009
DOI:10.1016/j.aca.2008.11.046
A novel and high throughput chemiluminescence (CL) method for determination of chemical oxygen demand (COD) in water sample was originally developed based on potassium permanganate–glutaraldehyde CL system. With this method, dissolved organic matter in water samples was digested by excess acid potassium permanganate, the reacted mixture solutions containing surplus KMnO4 were added in wells of a 96-well plate, followed by injection of glutaraldehyde in the wells, and CL was then produced along with the reaction of the added glutaraldehyde with the surplus KMnO4 and detected by a photomultiplier tube (PMT). The difference (ΔI) between the CL intensity for distilled water and that for sample water was proportional to the COD value of water sample. The calibration graph was linear in the range of 0.16–19.24 mg L−1 with a detection limit of 0.1 mg L−1. A complete analysis could be performed in 40 min including digestion and detection, giving a very high throughput of 3 × 96 samples in about 60 min. Compared with the conventional methods, this method is simple and sensitive and consumes very limited and cheap reagents. Owing to its rapid, automatic, high throughput and low cost characteristics, the presented CL method has been applied successfully to the determination of COD in real water samples (n = 32) with satisfactory results.
Co-reporter:Yi Wang, Yi Tao, Yunjin Lin, Liang Liang, Yi Wu, Haibin Qu, Tingbo Liang, Yiyu Cheng
Analytica Chimica Acta 2009 Volume 633(Issue 1) pp:65-70
Publication Date(Web):2 February 2009
DOI:10.1016/j.aca.2008.11.034
In this paper, we present a metabonomic method for the investigation of abnormal metabolic process in both serum and liver tissue of liver transplanted rats. Syngeneic transplantation was performed on male Lewis rats. The serum and grafted liver on day 1, 3, and 7 post-transplant were collected to analyze endogenous metabolites using gas chromatography coupled with mass spectrometry (GC–MS). The method was validated with acceptable linearity, precision, and repeatability. Thirty-four metabolites in serum and 29 metabolites in liver were identified. Results of correlation analysis illustrated metabolites with similar function exhibited similar variations in liver and serum. The data processed by principle component analysis (PCA) showed time-dependent biochemical variations. As a consequence, the present study may offer specific putative pathways in the pathophysiological mechanism of orthotopic liver transplantation.
Co-reporter:Peiying Shi;Qing He;Yufeng Zhang;Yiyu Cheng
Phytochemical Analysis 2009 Volume 20( Issue 3) pp:197-206
Publication Date(Web):
DOI:10.1002/pca.1115
Abstract
Introduction
Dibenzocyclooctadiene lignans are bioactive constituents in Schisandra chinensis (Turcz.) Baill. They are often present as isomers and this makes structural discrimination difficult.
Objective
To develop a rapid approach towards the characterisation and identification of isomeric dibenzocyclooctadiene lignans from S. chinensis using HPLC-PAD-ESI-MSn.
Methodology
The fragmentation behaviours of seven dibenzocyclooctadiene lignans from S. chinensis were studied using ion trap mass spectrometry with positive electrospray ionisation and loop injection. The fragmentation patterns of angeloylgomisin H, tigloylgomisin H, benzoylgomisin H and gomisin D were supported by high-resolution mass spectrometric analysis of some characteristic ions using a time-of-flight mass spectrometer. Combined with high-performance liquid chromatography and photodiode array detection, the established approach to the structural identification of dibenzocyclooctadiene lignans by ion trap mass spectrometry was applied to the analysis of extracts of S. chinensis.
Results
According to the HPLC retention behaviour, the diagnostic UV spectra and the molecular structural information provided by multistage mass spectrometry spectra and the literature, a total of 25 dibenzocyclooctadiene lignans, including seven groups of lignan isomers, were identified or tentatively characterised in S. chinensis rapidly. One of these was reported as a constituent of S. chinensis for the first time.
Conclusion
This study has shown that HPLC-PAD-ESI-MSn may be used as an effective and rapid method for the characterisation and identification of isomeric dibenzocyclooctadiene lignans from S. chinensis. Copyright © 2009 John Wiley & Sons, Ltd.
Co-reporter:Xintian Zheng, Jie Shen, Qiang Liu, Shufang Wang, Yiyu Cheng, Haibin Qu
Journal of Pharmaceutical and Biomedical Analysis 2009 49(2) pp: 481-486
Publication Date(Web):
DOI:10.1016/j.jpba.2008.10.018
Co-reporter:Jianyang Pan;Qiao Wang;Qing Shao;Yiyu Cheng
Chromatographia 2009 Volume 69( Issue 5-6) pp:445-451
Publication Date(Web):2009 March
DOI:10.1365/s10337-008-0915-9
A simple and rapid method using liquid chromatography-mass spectrometry was developed and applied to determine the concentration of huperzine A in rat plasma or cerebrospinal fluid following a single intravenous injection or nasal administration. The chromatographic separation of the analytes was performed by column switching. A Zorbax SB-C18 pre-column was used as the first column for sample clean-up, and then the analytes were eluted onto a Zorbax SB-C18 column, the second column, and detected by electrospray ionization MS using single ion monitoring in positive mode. Hup B was used as internal standard. Linear calibration curve was achieved over a dynamic range of 0.5–500 ng mL−1 for Hup A in plasma sample and 0.5–200 ng mL−1 in CSF sample. The inter- and intra-assay coefficients of variation for the analysis were within ±6.67%. The mean absolute recoveries of Hup A from plasma were between 94.7 and 106.7%.
Co-reporter:Hong Yao, Bin Wu, Yiyu Cheng, Haibin Qu
Food Chemistry 2009 115(1) pp: 380-386
Publication Date(Web):
DOI:10.1016/j.foodchem.2008.11.100
Co-reporter:Xiaofang Luo, Xiang Yu, Xiaoming Wu, Yiyu Cheng, Haibin Qu
Microchemical Journal 2008 Volume 90(Issue 1) pp:8-12
Publication Date(Web):October 2008
DOI:10.1016/j.microc.2008.02.005
A rapid and nondestructive near infrared spectroscopy (NIRS) was used to differentiate different geographical Paeoniae Radix and quantitatively predict the content of main active components. Paeoniflorin, albiflorin and benzoylalbiflorin were analyzed simultaneously with an Agilent Zorbax SB-C18 column by gradient elution under high-performance liquid chromatography-UV detection (HPLC-UV). Multiplicative scatter correction (MSC), first derivative and Savitsky–Golay were utilized together to correct the scattering effect and eliminate the baseline shift in all near infrared diffuse reflectance spectra in order to give a better correlation with the results obtained by HPLC-UV. Multiplicative regression methods were discussed. The spectra calibration equations produced highest correlation coefficient values (R2) and lowest root mean square error of prediction (RMSEP) were used for the determination of paeoniflorin, albiflorin and benzoylalbiflorin. The RMSEP of paeoniflorin, albiflorin and benzoylabiflorin were 0.866 mg/g, 0.369 mg/g and 0.084 mg/g, respectively, and the R2 of cross validation were 0.986, 0.939 and 0.971, respectively. Furthermore with the use of principle component analysis (PCA), Paeoniae Radix was clustered according to different cultivation area. The results indicated that the NIRS method could be used for the quality control of Chinese herbal medicine.
Co-reporter:Li LIU, Xiao-ping ZHAO, Di-feng ZHU, Yi-yu CHENG, Hai-bin QU
Chemical Research in Chinese Universities 2008 Volume 24(Issue 4) pp:420-426
Publication Date(Web):July 2008
DOI:10.1016/S1005-9040(08)60088-4
Co-reporter:Jin-zhong Xu;Jie Shen;Yi-yu Cheng;Hai-bin Qu
Journal of Zhejiang University-SCIENCE B 2008 Volume 9( Issue 9) pp:728-733
Publication Date(Web):2008 September
DOI:10.1631/jzus.B0820095
A high-performance liquid chromatographic (HPLC) method with ultraviolet (UV) detector had been developed for simultaneous quantification of danshensu, protocatechuic aldehyde, caffeic acid, salvianolic acid D, rosmarinic acid, salvianolic acid B and salvianolic acid A in Danshen injection. According to the UV spectra of these components, three detection wavelengths have been selected as follows: 280 nm for danshensu and protocatechuic aldehyde, 326 nm for caffeic acid, salvianolic acid D and rosmarinic acid, 286 nm for salvianolic acid B and salvianolic acid A. The limit of detection (LOD) was improved to be in the range of 0.008∼0.160 μg/ml. Moreover, excellent linear behavior over the investigated concentration range was observed, with R>0.999 for all the analytes.
Co-reporter:Yunfei Li;Yi Wang;Yiyu Cheng
Chromatographia 2008 Volume 67( Issue 3-4) pp:293-297
Publication Date(Web):2008 February
DOI:10.1365/s10337-007-0479-0
A high performance liquid chromatography coupled with ultraviolet detection and evaporative light scattering detection (HPLC-UV-ELSD) method was developed for simultaneously determining seven bioactive components, i.e. danshensu, protocatechuic aldehyde, salvianolic acid B, notoginsenoside R1, ginsenoside Rg1, ginsenoside Rb1, and astragaloside IV in “QI-SHEN-YI-QI” dropping pill, a widely used traditional Chinese medicine (TCM) for treating cardiovascular disease. The chromatographic separation was performed on a Zorbax Stable Bond C18 column using gradient elution with acetonitrile and water with acceptable validation results such as linearity and recovery. The recoveries of the seven investigated compounds ranged from 93.3 to 100.2% with RSD values less than 5%. More importantly, this proposed method was successfully used to determine the seven compounds in nine batches of “QI-SHEN-YI-QI” dropping pills, which indicated that the proposed method could be readily utilized as a quality control method for this TCM preparation.
Co-reporter:Peiying Shi, Qing He, Yue Song, Haibin Qu, Yiyu Cheng
Analytica Chimica Acta 2007 Volume 598(Issue 1) pp:110-118
Publication Date(Web):15 August 2007
DOI:10.1016/j.aca.2007.07.027
Flavonoid O-diglycosides are important bioactive compounds from genus Citrus. They often occur as isomers, which makes the structural elucidation difficult. In the present study, the fragmentation behavior of six flavonoid O-diglycosides from genus Citrus was investigated using ion trap mass spectrometry in negative electrospray ionization (ESI) with loop injection. For the flavonoid O-rutinosides, [M − H − 308]− ion was typically observed in the MS2 spectrum, suggesting the loss of a rutinose. The fragmentation patterns of flavonoid O-neohesperidosides were more complicated in comparison with their rutinoside analogues. A major difference was found in the [M − H − 120]− ion in the MS2 spectrum, which was a common feature of all the flavonoid O-neohesperidosides. The previous literature for naringin located the loss of 120 Da to the glycan part, whereas the present study for naringin had shown that the [M − H − 120]− ion was produced by a retro-Diels-Alder reaction in ring C, and this fragmentation pattern was confirmed by the accurate mass measurement using an orthogonal time-of-flight mass spectrometer. Combined with high performance liquid chromatography (HPLC) and diode array detection (DAD), the established approach to the structural identification of flavonoid O-diglycosides by ion trap mass spectrometry was applied to the analysis of extracts of two Chinese medicines derived from genus Citrus, namely Fructus aurantii and F. aurantii immaturus. According to the HPLC retention behavior, the diagnostic UV spectra and the molecular structural information provided by multistage mass spectrometry (MSn) spectra, 13 flavonoid O-glycosides in F. aurantii and 12 flavonoid O-glycosides in F. a. immaturus were identified rapidly.
Co-reporter:Yi-yu Cheng;Xiao-Ling Luo;Qing Shao;Hai-Bin Qu
Journal of Separation Science 2007 Volume 30(Issue 9) pp:1284-1291
Publication Date(Web):26 APR 2007
DOI:10.1002/jssc.200600450
By optimizing the extraction, separation, and analytical conditions, a reliable and accurate high-performance liquid chromatography method coupled with evaporative light scattering detection (ELSD) was developed for simultaneous determination of five terpenoids, i. e., triptolide, tripchlorolide, demethylzelastral, wilforlide B, and wilforlide A, in root, stem, leaves, root bark, twig, and root without bark of Tripterygium wilfordii Hook. f and six of its herbal preparations. This approach would thus provide a more accurate and general method for evaluating the quality of the herb and its preparations. Separation of these five terpenoids was achieved on a ZORBAX Eclipse XDB-C8 column with gradient elution using water and acetonitrile as solvents, both containing 0.05% formic acid, at a temperature of 30°C and a flow rate of 0.8 mL/min. The drift tube temperature of ELSD was set at 100°C, and the nitrogen flow rate at 1.5 L/min. Good linear relationships were obtained with correlation coefficients for the analytes exceeding 0.992, and the LOD and LOQ were less than 0.149 μg and 0.297 μg on column, respectively. Intra-day and inter-day precision of the analytes were less than 1.25% and 5.97%, respectively, and the average recovery rates obtained were in the range of 95.9 ± 3.7% to 100.4 ± 5.0% for all terpenoids with RSDs below 4.99%. Quantitative analysis of the five terpenoids in different parts of Tripterygium wilfordii and its six preparations showed that the contents of the terpenoids varied significantly. The tender root contained higher concentrations of triptolide, tripchlorolide, demethylzelastral, and wilforlide B than any other part of the herb. Correspondingly, the root bark contained the greatest concentration of wilforlide A, and the stem and twig came in second and third. This suggested that we could infer whether the medicinal materials were absolute roots without bark or not from the comparative contents of these terpenoids in the tablets in view of the fact that only the roots without bark are the valid officinal part of the plant. This method and the quantitation results obtained can provide a scientific and general as well as simple and convenient approach for the product manufacturers to set up quality control standards and for informing the public about the quality and safety of the preparations.
Co-reporter:Li Liu;Yun Lu;Qing Shao;Yi-Yu Cheng;Hai-Bin Qu
Journal of Separation Science 2007 Volume 30(Issue 16) pp:2628-2637
Publication Date(Web):14 SEP 2007
DOI:10.1002/jssc.200700214
Radix Ophiopogonis is a widely used traditional Chinese medicine. The quality of Radix Ophiopogonis available in the market varies, and some confusing or fake herbs exist. In order to improve the quality control of Radix Ophiopogonis, a novel fingerprinting method was established using HPLC coupled with UV and evaporative light-scattering detectors (ELSDs). Extraction with methanol and liquid–liquid extraction with water-saturated n-butanol were employed for the preparation of the sample solution. Chromatographic separation was performed on a Lichrospher C18 column (250×4.6 mm id, 5.0 μm particle size) with a linear gradient elution program. UV detection at 280 nm and evaporative light-scattering detection were utilized to obtain two subfingerprinting chromatograms. A novel protocol for data processing was proposed, in order to identify and remove redundant data obtained by the two detectors, and balance the weight of the two subfingerprints on the similarity values. The method was validated and applied to quality evaluation of 16 samples of Radix Ophiopogonis and related herbs.
Co-reporter:Xue-Jia Zhai;Hai-Bin Qu;Qing Shao;Yi-Yu Cheng
Chromatographia 2007 Volume 66( Issue 1-2) pp:43-47
Publication Date(Web):2007 July
DOI:10.1365/s10337-007-0253-3
A sensitive HPLC method based on post-column modification and fluorescence detection has been developed for determination of puerarin and daidzein in rat plasma. Chromatographic separation was performed on a C8 column with a linear gradient prepared from 0.5% aqueous acetic acid and 0.5% acetic acid in acetonitrile, delivered at a flow rate of 0.8 mL min−1. Naringin was used as the internal standard. It was necessary to use acetic acid in the mobile phase to achieve good separation, but this led to fluorescence signal suppression, because puerarin and daidzein have native fluorescence at pH 8.0–9.0. To enhance the sensitivity, post-column modification with alkaline buffer was adopted. After this modification, detection sensitivity for puerarin and daizein increased more than 500-fold and 600-fold, respectively, compared with direct fluorescence detection. Signal-to-noise ratios for detection for puerarin were more than 150 times better than for UV detection after use of the same method of sample preparation. This sensitive analytical method was successfully used to determine pharmacokinetic data for puerarin and daidzein in rat plasma after oral administration of a single dose of Puerariae radix extract containing puerarin (approx. 8.4 mg) and daizein (approx. 5.9 mg) to male SD rats.
Co-reporter:Xingchu Gong, Shichao Huang, Jianyang Pan, Haibin Qu
Chinese Journal of Chemical Engineering (January 2017) Volume 25(Issue 1) pp:68-73
Publication Date(Web):1 January 2017
DOI:10.1016/j.cjche.2016.06.005
In this work, the effects of degradation time, temperature, and pH value on the degradation of Salvianolic acid B in aqueous solution were determined. Higher pH values, higher extraction temperature, and longer extraction time led to more degradation of Salvianolic acid B. Danshensu concentration increased as Salvianolic acid B degraded. A mechanism model was developed considering the degradation of Salvianolic acid E and lithospermic acid, which were two degradation products of Salvianolic acid B. The reverse reactions of Salvianolic acid B degradation were also considered. Degradation kinetic constants were calibrated. The degradation kinetics of Salvianolic acid B, lithospermic acid, and Danshensu in a Salvia miltiorrhiza extract aqueous solution were predicted using the mechanism model. The predicted concentrations agreed well with the experimental results. This model was developed using degradation data obtained from simple composition systems, but it can be applied in a complex botanical mixture with high prediction accuracy.
Co-reporter:Cheng Jiang, Xingchu Gong, Haibin Qu
Separation and Purification Technology (15 September 2013) Volume 116() pp:287-293
Publication Date(Web):15 September 2013
DOI:10.1016/j.seppur.2013.05.049
•The adsorption efficiencies at the end of the process were predicted early-on.•Process parameters were adjusted according to the raw materials variation.•The strategy can lead the process towards the target adsorption efficiencies.The manufacturing process efficiencies and the products quality of herbal medicine often suffer from high variability with the variability of the raw materials. This paper presents a methodology for adjusting process parameters according to the raw materials variation for acceptable adsorption efficiencies during HM column chromatography process. The methodology was illustrated by an example of saponins adsorption process, which is a critical unit operation in macroporous resin column chromatography during Panax notoginseng injection manufacturing process. The impact of total saponins concentration in loading solution and adsorption time on adsorption efficiencies was mapped. The specification region of raw material was obtained and the adsorption efficiencies at the end of the adsorption process were predicted early-on. When the predicted adsorption efficiencies did not meet the target values, the control method proposed the use of an adjusted process parameter leading the adsorption process towards the target adsorption efficiencies at the end of the adsorption process. The results in this work facilitated the enhanced understanding of the relationships between raw material attributes, process parameters and saponins adsorption efficiencies. This case study demonstrated that it is possible to employ different process parameters to accommodate raw materials variation for acceptable process efficiencies.Graphical abstractThe adsorption efficiencies were predicted according to the raw materials variation and the process parameters were adjusted early-on, hence guiding the adsorption efficiencies towards the target values.Download full-size image
Co-reporter:
Analytical Methods (2009-Present) 2013 - vol. 5(Issue 2) pp:
Publication Date(Web):
DOI:10.1039/C2AY25925G
Very few efforts have been directed toward interpreting the differences between chromatographic and spectroscopic fingerprints for the purpose of quality control, although similarity analysis based on fingerprints is commonly applied to quality consistency evaluation of herbal medicines (HM). In the current study, comparative evaluation of high-performance liquid chromatography (HPLC), ultraviolet (UV), and near-infrared (NIR) fingerprint techniques combined with chemometric methods has been conducted to control the quality of Chinese herbal injections. A set of Danshen injections (DSI) are chosen as an example of the relevance to contemporary HM. Similarity analysis by principal component analysis, identification using linear discriminant analysis and k nearest neighbor classifiers, and control charts based on Hotelling's T2 and DModX statistics are employed to evaluate the quality consistency of the DSI samples from three different manufacturers. The results in this study demonstrate that the UV spectroscopy technique combined with chemometric methods is useful for the identity and consistency evaluation of DSI. Such an approach is believed to be equally applicable to other HM.
Co-reporter:
Analytical Methods (2009-Present) 2013 - vol. 5(Issue 17) pp:
Publication Date(Web):
DOI:10.1039/C3AY26540D
A data fusion method based on near infrared (NIR) spectra and ultraviolet (UV) spectra for simultaneous determination of six ginsenosides and four saccharides in Chinese herbal injection (CHI) was developed. Two data fusion strategies (low-level data fusion and mid-level data fusion) combined with partial least squares (PLS) regression and uninformative variable elimination by PLS (UVEPLS) regression were implemented, respectively. Compared with the models established by independent NIR or UV spectra, there was a significant improvement provided by two data fusion strategies, which benefited from the synergistic effect of complementary information obtained from near infrared spectroscopy (NIRS) and ultraviolet spectroscopy (UVS). The results in this work showed data fusion of NIR and UV spectra combined with a regression algorithm could be a promising strategy to determine the ginsenosides and saccharides in CHI rapidly and simultaneously.
Co-reporter:
Analytical Methods (2009-Present) 2014 - vol. 6(Issue 2) pp:NaN481-481
Publication Date(Web):2013/11/08
DOI:10.1039/C3AY41728J
The batch-to-batch quality consistency needs to be controlled to ensure the efficacy and safety of botanical drug products. Chromatographic fingerprinting is a powerful tool for characterizing complex chemical systems such as botanical drugs. This paper presented the combined use of a proposed weighting algorithm and multivariate statistical analysis on fingerprint data to achieve quality consistency evaluation of botanical drug products. A set of fingerprint data following multivariate normal distribution was simulated based on the real fingerprint data of a botanical drug product, Danshen injection. The weight of each peak was set based on its batch-to-batch peak variation. A principal component analysis (PCA) model was established, and the Hotelling T2 and DModX statistics were applied to evaluate quality consistency. The effect of weighting on the monitoring capability of the two statistics was evaluated through monitoring simulated peak area variations. The results showed that both the two statistics were more sensitive to the characteristic peaks with smaller batch-to-batch peak variations. Hence the peaks with larger variability will be permitted to have a wider tolerance range of variation, while a more narrow range of variation was seen for the peaks with smaller variability among batches. Peak weighting combined with multivariate statistical analysis has overcome some drawbacks of the fingerprint similarity analysis method, and is worthy of application and recommendation for the quality consistency evaluation of botanical drug products.
Co-reporter:
Analytical Methods (2009-Present) 2013 - vol. 5(Issue 2) pp:
Publication Date(Web):
DOI:10.1039/C2AY25705J
In traditional Chinese medicinal production, a high degree of batch-to-batch reproducibility is required to achieve successful batches that meet the quality standard of traditional Chinese medicinal preparations (TCMPs). In this paper, multivariate statistical process monitoring (MSPM) based on chromatographic fingerprinting has been introduced to evaluate the batch-to-batch reproducibility of TCMPs. A commonly used TCMP product, Sheng-Mai-Yin (SMY) oral liquid, is selected as a typical example to demonstrate the feasibility of this approach. A number of batches are prepared through normal operation procedures to simulate the common-cause variations induced by preparation days, herb materials, and operators. Another number of abnormal batches are designed to simulate different types of deviations, including the changes of herb material quality attributes and abnormal operation conditions. The high-performance liquid chromatographic fingerprinting is used to construct the integrative pattern of SMY products. A principle component analysis model is established of the fingerprint data of the normal batches. Multivariate (Hotelling T2 and DModX) control charts are successfully applied to monitor the abnormal batches. As an effective multivariate analysis method in this study, MSPM based on chromatographic fingerprinting promises great applications in batch monitoring and evaluation for the production of TCMPs.
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![(1R)-1,2,3,4,5,6-hexahydro-1,5-methano-8H-pyrido[1,2-a][1,5]diazocin-8-one](http://img.cochemist.com/ccimg/500/486-86-2.png)
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