Applying risk management to analytical methods for the desorbing process of ginkgo diterpene lactone meglumine injection / 中国天然药物

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.

Applying risk management to analytical methods for the desorbing process of ginkgo diterpene lactone meglumine injection / 中国天然药物

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.

Evaluate effects of different drying methods on quality of Tianshu capsule on substance basis / 中国中药杂志

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.

Studying on purification technology of Resina Draconis phenol extracts based on design space method / 中国中药杂志

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.

Impact of parameter fluctuations on the performance of ethanol precipitation in production of Re Du Ning Injections, based on HPLC fingerprints and principal component analysis / 中国天然药物

The present study was designed to determine the relationships between the performance of ethanol precipitation and seven process parameters in the ethanol precipitation process of Re Du Ning Injections, including concentrate density, concentrate temperature, ethanol content, flow rate and stir rate in the addition of ethanol, precipitation time, and precipitation temperature. Under the experimental and simulated production conditions, a series of precipitated resultants were prepared by changing these variables one by one, and then examined by HPLC fingerprint analyses. Different from the traditional evaluation model based on single or a few constituents, the fingerprint data of every parameter fluctuation test was processed with Principal Component Analysis (PCA) to comprehensively assess the performance of ethanol precipitation. Our results showed that concentrate density, ethanol content, and precipitation time were the most important parameters that influence the recovery of active compounds in precipitation resultants. The present study would provide some reference for pharmaceutical scientists engaged in research on pharmaceutical process optimization and help pharmaceutical enterprises adapt a scientific and reasonable cost-effective approach to ensure the batch-to-batch quality consistency of the final products.

Optimization of ultrasonic extraction process for Xiaoqinglong granules by Box-Behnken in condition of medium scale / 中国中药杂志

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.

Simultaneous Determination of Echinacoside, Acteoside and Isoacteoside in Total Cistanchis glycosides Capsules by HPLC / 世界科学技术-中医药现代化

This study was aimed to establish an HPLC method for simultaneous determination of the content of echinacoside, acteoside and isoacteoside in Total Cistanchis glycosides Capsules. Waters C18 column (4.6 mm ×150 mm, 5 μm) was used with the mobile phase of methanol-0.1% formic acid at a flow rate of 1.0 mL·min-1. The detection wavelength was set at 330 nm. The column temperature was maintained at 30℃ . The results showed that the linear ranges of echinacoside, acteoside and isoacteoside were in the range of 27.792-277.92 μg·mL-1 (r = 0.9996,n = 6), 2.4184-24.184 μg·mL-1 (r = 0.9996, n = 6), 5.106-51.06 μg·mL-1 (r = 0.9998, n = 6). The average recoveries of three components were in accordance with the determination requirement. It was concluded that the method was simple and accurate, which can be used in the content determination of echinacoside, acteoside and isoacteoside in Total Cistanchis glycosides Capsules.

Application of microwave technology in extraction process of Guizhi Fuling capsule / 中国中药杂志

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.

Optimization of vacuum belt drying process of Gardeniae Fructus in Reduning injection by Box-Behnken design-response surface methodology / 中国中药杂志

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.

Effects of ginkgo diterpene lactones meglumine injection's activated carbon adsorption technology on officinal components / 中国中药杂志

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.

Preparation of hydrophilic matrix sustained release tablets of total lactones from Andrographis paniculata and study on its in vitro release mechanism / 中国中药杂志

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.

Quality control in liquid-liquid extraction of Reduning injection using near-infrared spectroscopy technology / 中国中药杂志

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.

Determination of eleven major components and fingerprint chromatography for Reduning injection by UPLC / 中国中药杂志

A reliable method for simultaneous determinition of eleven representative components (neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, shanzhiside, geniposidic acid, genipin-1-β-D-gentiobioside, geniposide and secoxyloganin) in combination of chromatographic fingerpint analysis for Reduning injection was developed by ultra high-performance liquid chromatography (UPLC). The method was performed on an Agilent ZORBAX SB-C18 anlytical column (3. 0 mm x 100 mm, 1. 8 µm) with a guard column of Agilent UPLC Guard ZORBAX SB-C18 (3.0 mm x 5 mm) at the column temperature of 30 °C. The gradient mobile phase consisted of acetonitrile (A)-0. 1% phosphoric acid (B) with a flow rate of 0. 4 mL . min-1. The injection volumn was 2 µL. The detection wavelengths were set at 324 nm and 238 nm for quantit tive analysis and 225 nm for fingerpint chromatography. Neochlorogenic acid, chlorogenic acid, cryptochlorogenic acid, isochlorogenic acid B, isochlorogenic acid A, isochlorogenic acid C, shanzhiside, geniposidic acid, genipin-1-β-D-gentiobioside, geniposide and secoxyloganin were baseline seperated with good linearity relationships (r >0. 999) between concentration and peak areas over the linear ranges. The average recoverys of the investigated compounds were 103.5%, 100. 2%, 103. 3%, 102. 8%, 101. 3%, 102. 8%, 97. 36%, 99. 62%, 98. 16%, 102. 8%, 99. 27%, respectively. Reduning injection of forty-five batches was analyzed by UPLC finge print chromatography. Thirty batches were selected to generate the reference fringerprint chromatography with fourteen common peaks. The similarity values between the reference fringerprint chromatography and the remaining fifteen batches were higher than 0. 99. The developed method was fast, accurate and sensitive. It could be used as a reference for the quality control of multiple components determination and fingerprint chromatography for Reduning injection in future.

Near infrared spectroscopy on-line and real-time monitoring of alcohol precipitation process of reduning injection / 中国中药杂志

Near infrared (NIR) spectroscopy as a kind of rapid process analysis technology has been successfully applied in Chinese medicine pharmaceutical process. In this research, the technology was adopted to establish the rapid quantitative analysis models of main indicators from the Lonicera japonica and Artemisia annua alcohol precipitation process of Reduning injection. On-line NIR spectra of 142 samples from alcohol precipitation process were collected and the content of main indicators for each sample were detected through off-line HPLC. With eliminating outliers, determination of spectra pretreatment method and selecting optimal band, the NIR quantitative calibration model for each indicator was established using partial least squares (PLS). These models were used to predict the unknown samples from precipitation process of Reduning injection to achieve the goal of rapid detection. The results showed that the models were ideal. The correlation coefficients of models for neochlorogenic acid, chlorogenic acid, 4-O-caffeoylquinic acid and secoxyloganin were 0.973 872, 0.985 449, 0.975 509 and 0.979 790, respectively and their relative standard errors of prediction (RSEP) were 2.922 49%, 2.341 37%, 2.930 40% and 2.184 60%, respectively. This study indicated that the NIR quantitative calibration model showed good stability and precision, and it can be used in rapid quantitative detection of main indicators of efficacy in order to on-line monitor the alcohol precipitation process of Reduning injection.

HPLC fingerprint of liuwei dihuang soft capsule / 中国中药杂志

In order to establish HPLC fingerprint of Liuwei Dihuang soft capsule, and to provide certain reference for an quality control of it, the HPLC method was performed on an Agilent C18 (4.6 mm x 250 mm, 5 μm) column with acetonitrile-0.02% trifluoroacetic acid as mobile phase, gradient elution volume flow of 1.0 mL x min(-1), column temperature was 30 degrees C, detection wavelength: 0-60 min, 238 nm, 60-70 min, 210 nm. The software for chromatographic fingerprint was applied to analysis different batches of Liuwei Dihuang soft capsule samples. Sixteen mutual peaks were selected as the fingerprint peaks in 12 samples with loganin as the reference peak, and all of the detected peaks were separated effectively. Cluster analysis (HCA) and similarity analysis (SA) were done based on data of 12 samples clustering analysis of 12 batches of samples were divided into 2 categories. Including 7 for the first class, the rest was second, similarities calculated by SA were all above 0.92, indicating a good similarity between the reference and twelve batches of samples, also, the analysis results of HCA and SA basically the same. This method is simple with good precision, repeatability and stability, and provides the basis for Liuwei Dihuang soft capsule quality control.

Rapid identification of six chemical constituents in Guizhi Fuling capsule by DART-Q-TOF-MS / 中国中药杂志

In order to establish a rapid method for identifying six constituents in Guizhi Fuling capsule, Q-TOF with DART ion source was used to perform the direct analysis of compounds in Guizhi Fuling capsule. The DART sampler delivery rate was 0.2 mm s(-1). The temperature of helium gas of DART was 450 degrees C. The capillary voltage was kept at 1 000 V. The temperature of the drying gas of Agilent 6538 Q-TOF MS was set at 350 degrees C. The flow rate of the drying gas of MS was set at 3.5 L x min(-1). The MS scan range was m/z 50-1 000. Based on accurate mass measurements and the elemental compositions of the product ions and fragmentation patterns of reference conpounds, six components, amygdalin, paeonol, paeoniflorin, cinnamic acids, gallic acid, benzoic acid were identified rapidly. The method can rapidly identify six chemical constituents in three batch of Guizhi Fuling capsule. The DART-Q-TOF-MS method is simple, rapid and specific and it can be used for rapid identification and characterization of compounds in traditional Chinese medicines.

Quality evaluation of guizhi fuling capsule using self-control method of reference Chinese medicine preparation / 中国中药杂志

Taking guizhi fuling capsule (GZFL) for instance, a new method about reference Chinese medicine preparation which was used as standard substance for the quality evaluation of complex Chinese medicine preparation by the fingerprint of reference preparation instead of standard fingerprint was proposed. It could eliminate the errors from different instruments, chromatographic columns and solve the problem of similarity matching in the absence of standard fingerprint. The qualification of reference GZFL was evaluated according to the quality control method of GZFL from Chinese Pharmacopoeia. Then multiple batches of GZFL were estimated, taking fingerprint of reference preparation and standard fingerprint as references, respectively, at different instruments and chromatographic columns. Finally, the packaging and expiration date for reference GZFL were confirmed according to the results of stability investigation. The results indicated that the fingerprint of reference GZFL could be used to assess the quality of GZFL better than standard fingerprint. The data of accelerated stability and long-term stability test demonstrated that reference GZFL was stable in the conditions of double blister package. Therefore, reference GZFL can be used as standard substance in quality control of GZFL.

Study on HPLC fingerprint of triterpene acids in different medicinal parts of Poria / 中国中药杂志

<p><b>OBJECTIVE</b>To establish an analytical method for the fingerprint of triterpenoid constituents of Poria by HPLC and compare the fingerprints of different medicinal parts of Poria in order to provide basis for controlling Poria quality.</p><p><b>METHOD</b>The HPLC chromatographic conditions were Waters Symmetry C18 column (4.6 mm x 250 mm, 5 μm), 0.1% phosphoric acid (A) and acetonitrile (B) as gradient mobile phases, flow rate being 1.0 mL x min(-1), column temperature at 30 degrees C, The detection wavelength was set at 210 nm; The cluster analysis was carried on by SPSS 15.0.</p><p><b>RESULT</b>The HPLC fingerprints of triterpenoid constituents of Poria were set up. There were 16 common peaks in different medicinal parts. The results of method validation met technical requirement of fingerprints; Triterpenoid constituents in White Poria and Poria cum Radix Pini were different from Poria. The content of pachymic acid was the highest in Poria. The effect of habitat on the quality was no obvious difference.</p><p><b>CONCLUSION</b>The method is stable, reliable, reproducible, and can be used as an effective means of Poria quality evaluation.</p>

Determination of polysorbate 80 in Reduning injection by HGPC-ELSD / 中国中药杂志

<p><b>OBJECTIVE</b>To establish the method for determining polysorbate 80 in Reduning injection by HPLC-ELSD, and to control the mass of polysorbate 80 in Reduning injection.</p><p><b>METHOD</b>It was performed by HGPC-ELSD with TOSHTSK-GEL G4000PWxl (7.8 mm x 300 mm, 10 μm). Water was used as mobile phase, the flow rate was 0.7 mL x min(-1), and the temperature was set at 30°C. The evaporated light scattering detector was adopted. The drift tube temperature was 55°C, and nitrogen was used as carrier gas, with the flow rate of 2.0 L x min(-1) and gain of 1.0.</p><p><b>RESULT</b>The calibration curve showed good linearity of polysorbate 80 in the test range from 1.01 to 15.20 g x L(-1) (r2 = 0.999 3). The recovery rate was 98.10% with RSD of 2.0%.</p><p><b>CONCLUSION</b>The method is simple, rapid, accurate and reliable and suitable for the determination of polysorbate 80 in Reduning injection.</p>

Application of near-infrared spectroscopy technology in extraction and concentration process of Reduning injection / 中国中药杂志

<p><b>OBJECTIVE</b>To establish a rapid quantitative analysis method for the content of chlorogenic acid and solid content in the extraction liquid concentration process during the production of Reduning injection by using the near-infrared (NIR) spectroscopy, in order to reflect the concentration state in a real-time manner and really realize the quality control of concentrating process of the extraction and concentration process.</p><p><b>METHOD</b>The samples during the Jinqing extraction liquid concentration process were collected. After the removal of abnormal samples, the spectra pretreatment and the wave band selection, the quantitative calibration model between NIR spectra and chlorogenic acid HPLC analytical value and solid content was established by using PLS algorithm, and unknown samples were predicted.</p><p><b>RESULT</b>The correlation coefficients between the chlorogenic acid content and the solid content were respectively 0.992 1 and 0.994 0, and the correlation coefficients of the verification model were respectively 0.994 4 and 0.998 4, with the root mean square error of calibration (RMSEC) of 0.814 6 and 2.656 1 and the root mean square error of prediction (RMSEP) of 0.704 6 and 1.876 7 respectively, and the relative standard errors of predictions (RSEP) were 6.01% and 2.93% respectively.</p><p><b>CONCLUSION</b>The method is simple, rapid, nondestructive, accurate and reliable, thus could be adopted for the fast monitoring of the chlorogenic acid content and the solid content during the concentration process of Reduning injection extraction liquid.</p>