Analysis errors can occur in the desorbing process of ginkgo diterpene lactone meglumine injection（GDMI） by a conventional analysis method, due to several factors, such as easily crystallized samples, solvent volatility, time-consuming sample pre-processing, fixed method, and offline analysis. Based on risk management, near-infrared（NIR） and mid-infrared（MIR） spectroscopy techniques were introduced to solve the above problems with the advantage of timely analysis and non-destructive nature towards samples. The objective of the present study was to identify the feasibility of using NIR or MIR spectroscopy techniques to increase the analysis accuracy of samples from the desorbing process of GDMI. Quantitative models of NIR and MIR were established based on partial least square method and the performances were calculated. Compared to NIR model, MIR model showed greater accuracy and applicability for the analysis of the GDMI desorbing solutions. The relative errors of the concentrations of Ginkgolide A（GA） and Ginkgolide B（GB） were 2.40% and 2.89%, respectively, which were less than 5.00%. The research demonstrated the potential of the MIR spectroscopy technique for the rapid and non-destructive quantitative analysis of the concentrations of GA and GB.

The "design space" method was used to optimize the purification process of Resina Draconis phenol extracts by using the concept of "quality derived from design" (QbD). The content and transfer rate of laurin B and 7,4'-dihydroxyflavone and yield of extract were selected as the critical quality attributes (CQA). Plackett-Burman design showed that the critical process parameters (CPP) were concentration of alkali, the amount of alkali and the temperature of alkali dissolution. Then the Box-Behnken design was used to establish the mathematical model between CQA and CPP. The variance analysis results showed that the P values of the five models were less than 0.05 and the mismatch values were all greater than 0.05, indicating that the model could well describe the relationship between CQA and CPP. Finally, the control limits of the above 5 indicators (content and transfer rate of laurine B and 7,4'-dihydroxyflavone, as well as the extract yield) were set, and then the probability-based design space was calculated by Monte Carlo simulation and verified. The results of the design space validation showed that the optimized purification method can ensure the stability of the Resina Draconis phenol extracts refining process, which would help to improve the quality uniformity between batches of phenol extracts and provide data support for production automation control.

To investigate the effect of hot air circulation drying and spray drying on the quality of Tianshu capsule from the view point of chemical compositions. UPLC-DAD was used to establish the fingerprint of Tianshu capsules for the first time, and the main chemical constituents were identified by UPLC-Q-TOF-MS/MS. A total of 62 compounds were identified in this method, 21 of which were reported in Tianshu capsules for the first time. The results showed that there were no significant differences in the identification of the chemical constituents types between these two methods, but the contents of some constituents were different. The common patterns generated by the 10 batches of hot air cycle drying samples were used as the control fingerprint, and the similarity of the spray drying samples fingerprints was 0.877, with high similarity of the fingerprints between these two methods. UPLC-DAD combined with UPLC-Q-TOF-MS/MS technology was used for the first time to evaluate the chemical constituents of Tianshu capsule rapidly, comprehensively and accurately, providing technical support for the quality evaluation of Tianshu capsule.

Objective To develop a multivariate statistical process control (MSPC) model for in-line monitoring of the extraction process ofLonicerae Japonicae Flos (LJF).Methods The spectral data collected by near infrared spectrascopy coupled with MSPC technique were applied to establish the statistical model.Three kinds of multivariate control charts (PC scores,Hottelling T2 and DModX) were used to monitor the abnormal variations caused by the change of starting material quality attributes and abnormal operation conditions.Moreover,the extraction process trajectory was developed by applying principal component analysis on the process spectra,reflecting the changing trend with extraction time.Results The MSPC model with good repeatability and robustness could show the quality variation of extraction process of LJF and accurately predict the normal batches.The joint use of three control charts could effectively identify the abnormal conditions.Compared with the traditional monitoring methods,this approach was fast and nondestructive,and can implemente the in-line and real-time monitoring.Conclusion The near infrared spectroscopy combined with MSPC can be successfully applied to the extraction processes of LJF,which is of great significance for the improvement of the quality control of Chinese material medica (CMM).

This paper is to investigate the optimization conditions of ultrasonic technique for extraction process of Xiaoqinglong granules in medium scale. First of all, single factor experiment was used to determine the overall impact tendency and range of each factor； secondly, Box-Behnken method was used for optimization and detecting the content of paeoniflorin, ephedrine hydrochloride, glycyrrhizic acid of the liquid medicine. Their respective extraction rate was calculated and the comprehensive evaluation was carried out. The results were used as the evaluation basis for the efficacy of Xiaoqinglong granules ultrasonic extraction. The test results showed that the optimum extraction process of Xiaoqinglong granules by ultrasonic extraction was under the following conditions: ultrasonic power 600 W, liquid-solid ratio 10∶1, extraction for 31 min. Under this condition, the predicted value of extraction rate for Xiaoqinglong granules was 85.90%, and the test value was 85.87%. The mathematical model(P<0.01) established in this paper was significant, and can be used for the analysis and prediction of the ultrasonic extraction process of Xiaoqinglong granules.

The invention discloses a rapid quantitative detection method for a sweet wormwood and honeysuckle alcohol precipitation concentration process. The rapid quantitative detection method comprises the following steps: collecting sweet wormwood and honeysuckle alcohol precipitation concentrated liquid samples of different batches in large-scale production of redlining injection; measuring key indicators of the sweet wormwood and honeysuckle alcohol precipitation concentrated liquid samples; acquiring near infrared spectrum charts of the sweet wormwood and honeysuckle alcohol precipitation concentrated liquid samples; respectively establishing quantitative correction models by selecting a suitable spectrum pre-processing method and a suitable modelling wave band, and inspecting the performance of a model by taking model cross validation correlation coefficients, cross validation mean square root errors, and relative deviation evaluation indexes between predicted values and offline detection values to establish the rapid quantitative detection method for the sweet wormwood and honeysuckle alcohol precipitation concentration process. According to the rapid quantitative detection method, a sample quantitative correction model for the sweet wormwood and honeysuckle alcohol precipitation concentration process is established by introducing a near infrared spectrum technology, so that the changes of the densities of neochlorogenic acid, chlorogenic acid and cryptochlorogenic acid in the samples in the sweet wormwood and honeysuckle alcohol precipitation concentration process are detected rapidly and quantatively; the established analysis method is rapid and green, and can be applied to online detection in a production process.

Ginkgo terpene lactone raw material (GTL) is extracted and purified from the dry leaves of Ginkgo biloba L., and it is the raw material in ginkgo diterpene lactone meglumine injections for treating patients suffering from mild to moderate cerebral infarction (manufactured by Jiangsu Kanion Pharmaceutical Co., Ltd., Lianyungang, Jiangsu, China). In the present study, an efficient strategy was developed for the characterization and identification of chemical components in GTL using high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (HPLC/Q-TOF MS/MS) combined with online valve switching. The structures of compounds were elucidated based on the accurate mass measurements, the fragmentation patterns of standards and the fragment ion at m/z 57.0700 of the tert-butyl group. As a result, 12 ginkgo terpene lactones were screened and identified from GTL, including ginkgolide A, B, C, J, M, K, L, Q, and P as well as bilobalide, one isomer of ginkgolide C and one isomer of ginkgolide A. Furthermore, four main ginkgolides (ginkgolide A, B, C and K) were simultaneously determined using a high performance liquid chromatograph coupled with a diode-array detector and an evaporative light scattering detector method (HPLC-DAD-ELSD) for the first time. The quantitative analytical method was fully validated with respect to linearity (r(2) > 0.998), sensitivity, precision, accuracy (the recovery was between 99.7% and 100.4%), and robustness. Ten batches of samples were detected by HPLC-DAD-ELSD, indicating that the proposed approach was applicable for the evaluation of GTL quality.

In this paper, optimization of the conditions of microwave technique in extraction process of Guizhi Fuling capsule in the condition of a pilot scale was carried out. First of all, through the single factor experiment investigation of various factors, the overall impact tendency and range of each factor were determined. Secondly, L9 (3(4)) orthogonal test optimization was used, and the contents of gallic acid in liquid, paeoniflorin, benzoic acid, cinnamic acid, benzoyl paeoniflorin, amygdalin of the liquid medicine were detected. The extraction rate and comprehensive evaluation were calculated with the extraction effect, as the judgment basis. Theoptimum extraction process of Guizhi Fuling capsule by microwave technology was as follows: the ratio of liquid to solid was 6: 1 added to drinking water, the microwave power was 6 kW, extraction time was 20 min for 3 times. The process of the three batch of amplification through verification, the results are stable, and compared with conventional water extraction has the advantages of energy saving, time saving, high efficiency advantages. The above results show the optimum extracting technology of high efficiency, stable and feasible.

With the diversion rate of ginkgolide A, B, K as comprehensive evaluation indexes, the amount of activated carbon, ad- sorption time, mix rate, and adsorption temperature were selected as factors, orthogonal design which based on the evaluation method of information entropy was used to optimize activated carbon adsorption technology of ginkgo diterpene lactones meglumine injection. Opti- mized adsorption conditions were as follows: adsorbed 30 min with 0.2% activated carbon in 25 °C, 40 r ·min⁻¹, validation test re- sult display. The optimum extraction condition was stable and feasible, it will provide a basis for ginkgo diterpene lactone meglumine injection' activated carbon adsorption process.

Objective To establish a method for the determination of fructose and glucose by HPLC- ELSD in Reduning injection. Methods The aminopropyl column was used with acetonitrile: water( 83∶ 17) as mobile phase at a flow rate of 0. 7 m L / min and ELSD detector,the flow rate was 1. 2ml / min. Results The calibration linear curves of fructose and glucose were within concentrations of 0. 4056 ~ 4. 056 g and 0. 8348 ~ 8. 348 g. The average recoveries of fructose and glucose were 102. 3% and 102.0%,RSD were 2. 8% and 2. 9% respectively. Conclusion This method is simple,quick and specific,and suitable for the quality control both of the components in Reduning injection.

A high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC/Q-TOF MS) was developed for the analysis of chemical composition change in the production process of Re Du Ning injection, a Chinese medicine preparation with a combination of Lonicera japonica Thunb., Gardenia jasminoides Ellis and Artemisia annua L. A total of 90 compounds from raw materials-intermediates-Re Du Ning injection were detected; among them, 55 compounds were identified or tentatively characterized, and the characteristic ions of different types of compounds were described. Based on these studies, the different types of compounds in the various process routes were analyzed. A total of 28 compounds, including seven iridoid glycosides and six monoterpenes from G. jasminoides Ellis, five iridoid glycosides, nine phenolic acids and one unknown compound from L. japonica Thunb., were transferred to Re Du Ning injection, and two unknown compounds were generated in the production process of Re Du Ning injection. The results indicated that the Chinese Medicine Pharmaceutical process control is very important. This method could provide some reference for other Chinese medicine preparations.

To optimize the belt drying process conditions optimization of Gardeniae Fructus extract from Reduning injection by Box-Behnken design-response surface methodology, on the basis of single factor experiment, a three-factor and three-level Box-Behnken experimental design was employed to optimize the drying technology of Gardeniae Fructus extract from Reduning injection. With drying temperature, drying time, feeding speed as independent variables and the content of geniposide as dependent variable, the experimental data were fitted to a second order polynomial equation, establishing the mathematical relationship between the content of geniposide and respective variables. With the experimental data analyzed by Design-Expert 8. 0. 6, the optimal drying parameter was as follows: the drying temperature was 98.5 degrees C , the drying time was 89 min, the feeding speed was 99.8 r x min(-1). Three verification experiments were taked under this technology and the measured average content of geniposide was 564. 108 mg x g(-1), which was close to the model prediction: 563. 307 mg x g(-1). According to the verification test, the Gardeniae Fructus belt drying process is steady and feasible. So single factor experiments combined with response surface method (RSM) could be used to optimize the drying technology of Reduning injection Gardenia extract.

This study aimed to monitor liquid-liquid extraction of Gardenia jasminoides Ellis (Zhizi in Chinese) using in-line near-infrared spectroscopy. Shanzhiside (SZS), deacetyl asperulosidic acid methyl ester (DAAME), genipin-1-β-D-gentiobioside (GG), geniposide (GS), total acids (TA) and soluble solid content (SSC) were selected as quality control indicators, and measured by reference methods. Both partial least-squares regression (PLSR) and back propagation artificial neural networks (BP-ANN) were applied to create models to predict the content of above indicators. Paired-samples t-test and nonparametric test were used to compare differences in predictive values between two models of each indicator. Relative standard error of prediction (RSEP) and mean absolute percentage error (MAPE) were used to evaluate the predictive accuracy of the established models. The results showed that there was no significant difference in predicting DAAME, GS and TA between two models. However, PLSR model gave better accuracy in predicting GG and SZS than BP-ANN model. The BP-ANN model of SSC was better than PLSR model. This study shows that NIR spectroscopy can be used for rapid and accurate analysis of quality control indicators in the liquid-liquid extraction of Zhizi. Simultaneously, this study can serve as technical support for the application of NIR spectroscopy in the industrial production process.

Objective Near-infrared(NIR) spectroscopy was used to rapidly determine the concentration of chlorogenic acid(CA) and soluble solid content in alcohol precipitation of Lonicerae Japonicae Flos and Artemisiae Annuae Herba(LA) in Reduning Injection, so as to increase the level of quality control of alcohol precipitation process. Methods The LA samples of alcohol precipitation were collected. The PLS algorithm was used to establish NIR models between spectra and concentration of CA and total solid content, and the concentration of CA and soluble solid content in unknown batch were predicted. Results The correlation coefficients(R) of NIR models were above 0.980 in calibration sets. The R of verification model was above 0.980, the root mean square error of prediction(RMSEP) for CA and soluble solid content were 0.541 and 0.218, respectively, and the relative standard errors(RSEP) for CA and soluble solid content were no more than 8%. Conclusion The results demonstrate that NIR could determine the concentration of CA and soluble solid content in alcohol precipitation of Reduning Injection rapidly and accurately.

Ethnopharmacological relevance: Re Du Ning Injection (RDN), a traditional Chinese medicine injection, is made from the extracts of Lonicerae japonicae flos (LJF), Artemisiae annuae herba (AAH) and Gardeniae fructus (GF). Since last decade, RDN has been widely used in China for the treatment of fever, inflammation, allergy and viral infection.Aim of the study: To elucidate the potential influences of RDN on the activities of four cytochrome P450 (CYP) isozymes in rats (CYP1A2, CYP2C11, CYP2D1 and CYP3A1/2) by "cocktail method".Materials and methods: A sensitive and specific LC-MS method capable of simultaneous quantification of four substrates and their metabolites in rat plasma was developed and validated. Relative activity estimation of four isozymes was carried out by comparing plasma pharmacokinetics of substrates and their metabolites (phenacetin/ paracetamol for CYP1A2, tolbutamide/4-hydroxytolbutamide for CYP2C11, dextromethorphan/ dextrorphan for CYP2D1 and dapsone/N-acetyl dapsone for CYP3A1/2) between control and RDN treatment groups.Results: Compared with control group, RDN at different levels could increase the total amount of tolbutamide, dextromethorphan and dapsone absorbed into blood, while decrease the total amount of phenacetin absorbed into blood at low and medium dosage and increase it at high dosage.Conclusions: RDN could inhibit the activities of CYP2C11, CYP2D1 and CYP3A1/2, induce the activity of CYP1A2 at low and medium dosage but inhibit it at high dosage. The results indicated that drug co-administrated with RDN may need dose adjustment. (C) 2015 Elsevier Ireland Ltd. All rights reserved.

Quantitative models were established to analyze the content of chlorogenic acid and soluble solid content in the liquid-liquid extraction of Reduning injection by near-infrared (NIR) spectroscopy. Seven batches of extraction solution from the liquid-liquid extraction of Lonicerae Japonicae Flos and Artemisiae Annuae Herba were collected and NIR off-line spectra were acquired. The content of chlorogenic acid and soluble solid content were determined by the reference methods. The partial least square (PLS) and artificial neural networks (ANN) were used to build models to predict the content of chlorogenic acid and soluble solid content in the unknown samples. For PLS models, the R2 of calibration set were 0.9872, 0.9812, RMSEC were 0.1533, 0.7943, the R2 of prediction set were 0.9837, 0.9733, RMSEP were 0.2464, 1.2594, RSEP were 3.25%, 3.31%, for chlorogenic acid and soluble solid content, respectively. For ANN models, the R2 of calibration set were 0.9903, 0.9882, RMSEC were 0.0974, 0.4543, the R2 of prediction set were 0.9868, 0.9699, RMSEP were 0.1920, 0.9427, RSEP were 2.61%, 2.75%, for chlorogenic acid and soluble solid content, respectively. Both the RSEP values of chlorogenic acid and soluble solid content were lower than 6%, which can satisfy the quality control standard in the traditional Chinese medicine production process. The RSEP values of ANN models were lower than PLS models, which indicated the ANN models had better predictive performance for chlorogenic acid and soluble solid content. The established method can rapidly measure the content of chlorogenic acid and soluble solid content. The method is simple, accurate anc reliable, thus can be used for quality control of the liquid-liquid extraction of Reduning injection.

The caffeoylquinic acids (CQAs) are one important group with various biological activities of natural products in herbal medicines and food plants. This finding caused new interest in the properties and thermal stability of CQAs, since many processing and preparation of pharmaceutical and foodstuffs involved liquid extraction and heating procedure. A rapid-resolution liquid chromatography method coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry has been developed to research the thermal stability and transformation products of the six CQAs, 5-O-CQA, 3-O-CQA, 4-O-CQA, 3, 4-O-di-CQA, 4, 5-O-di-CQA and 3, 5-O-di-CQA, in water by heating an aqueous solution of each compound in the boiling water for 0–6 h. The order of thermal stability is 5-O-CQA > 3-O-CQA > 4-O-CQA for mono-CQAs. However, it is different with the research results reported by Kuhnert et al.: When the mono-CQAs were treated with aqueous tetramethylammonium hydroxide (pH 12) at the room temperature, the order of the stability is 5-O-CQA > 4-O-CQA > 3-O-CQA in terms of the hydrolysis of the caffeoyl ester. For di-CQAs, the order of thermal stability is 4, 5-O-di-CQA > 3, 5-O-di-CQA > 3, 4-O-di-CQA during heated in the boiling water bath. The mono-CQAs undergo transformations such as isomerization, hydroxylation and/or transformation to caffeic acid and quinic acid. The di-CQAs could isomerize to each other and degrade to mono-CQAs, caffeic acid and the compounds with the formula of C15H14O6. It is useful for researchers to choose the proper sample procedure (extraction method and time) and investigate plant metabolism.

Recently, chromatographic fingerprinting has become one of the most powerful approaches for quality control of Chinese herbal preparations.

In this study, hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata were prepared and the in vitro release behavior were also evaluated. The optimal prescription was achieved by studying the main factor of the type and amount of hydroxypropyl methylcellulose (HPMC) using single factor test and evaluating through cumulative release of three lactones. No burst drug release from the obtained matrix tablets was observed. Drug release sustained to 14 h. The release mechanism of three lactones from A. paniculata was accessed by zero-order, first-order, Higuchi and Peppas equation. The release behavior of total lactones from A. paniculata was better agreed with Higuchi model and the drug release from the tablets was controlled by degradation of the matrix. The preparation of hydrophilic matrix sustained release tablets of total lactones from A. paniculata with good performance of drug release was simple.

BACKGROUND:Liquid-liquid extraction of Lonicera japonica and Artemisia annua (JQ) plays a significant role in manufacturing Reduning injection. Many process parameters may influence liquid-liquid extraction and cause fluctuations in product quality.OBJECTIVE:To develop a near-infrared (NIR) spectroscopy method for on-line monitoring of liquid-liquid extraction of JQ.MATERIALS AND METHODS:Eleven batches of JQ extraction solution were obtained, ten for building quantitative models and one for assessing the predictive accuracy of established models. Neochlorogenic acid (NCA), chlorogenic acid (CA), cryptochlorogenic acid (CCA), isochlorogenic acid B (ICAB), isochlorogenic acid A (ICAA), isochlorogenic acid C (ICAC) and soluble solid content (SSC) were selected as quality control indicators, and measured by reference methods. NIR spectra were collected in transmittance mode. After selecting the spectral sub-ranges, optimizing the spectral pretreatment and neglecting outliers, partial least squares regression models were built to predict the content of indicators. The model performance was evaluated by the coefficients of determination (R (2)), the root mean square errors of prediction (RMSEP) and the relative standard error of prediction (RSEP).RESULTS:For NCA, CA, CCA, ICAB, ICAA, ICAC and SSC, R (2) was 0.9674, 0.9704, 0.9641, 0.9514, 0.9436, 0.9640, 0.9809, RMSEP was 0.0280, 0.2913, 0.0710, 0.0590, 0.0815, 0.1506, 1.167, and RSEP was 2.32%, 4.14%, 3.86%, 5.65%, 7.29%, 6.95% and 4.18%, respectively.CONCLUSION:This study demonstrated that NIR spectroscopy could provide good predictive ability in monitoring of the content of quality control indicators in liquid-liquid extraction of JQ.