Pengcheng Guo,Qizheng Wang,Xiaoqiang Xiang,Yufeng Zhang,Yue Pan,Zhong Zuo,Jianxin Wang
In this study, a multi-component integrated dissolution evaluation system of Yuanhu Zhitong tablets (YZTs) was established based on in vitro and in vivo correlation (IVIVC). The dissolution tests of five quality markers (Q-markers), including tetrahydropalmatine, α-allocryptopine, protopine, corydaline, and byakangelicin, in YZTs were conducted under different dissolution conditions, and pharmacokinetic studies were performed in beagle dogs to construct a correlation model using numerical deconvolution. The data of the five ingredients were integrated in vitro and in vivo according to the biopharmaceutical classification system (BCS) to establish an IVIVC integrating multiple Q-markers. The dissolution media with the best correlation of components were obtained and validated. The results showed that all five components were classified as BCS I compounds, and α-allocryptopine, byakangelicin, tetrahydropalmatine, and corydaline showed good correlation in the paddle method, 75 rpm, with dissolution media of artificial gastric fluid, acetate buffer, acetate buffer and 0.1 M HCl, respectively. Protopine showed good correlation in the paddle method, 100 rpm, with dissolution media of 0.1 M HCl. The integrated BCS I Q-markers showed the best correlation in the medium of acetate buffer. The multi-component integrated dissolution evaluation system established in this experiment accurately predicted the pharmacokinetic data of YZTs by verifying the media, which can be used for the quality control of YZTs. The present study provides an effective and promising strategy for the dissolution evaluation for traditional Chinese medicine preparations.
Chiral compounds commonly exist in traditional Chinese medicine (TCM), but little research on the quality control of TCM has been conducted. In this study, a new strategy is proposed, taking Yuanhuzhitong tablet [YHZT, consisting of Radix Angelicae Dahuricae and Rhizoma Corydalis (Yan Hu Suo, YHS)] for example, which is based on chiral isomer ratio analysis to monitor the production process of Chinese patent medicine companies. In the process of content determination for tetrahydropalmatine (THP) in YHZT from different companies, noticeable differences were observed in their chromatographic behaviors. It is known that THP has two enantiomers, naturally coexisting in YHS as a racemic mixture, so we prepared THP twice and subsequently performed chiral separation analysis using supercritical fluid chromatography. As a result, the peak area ratios of two enantiomers from different companies varied remarkably, demonstrating that some companies did not probably manufacture YHZT products in accordance with the prescription proportion, used inferior or extracted YSH crude materials in the production process, and added raw chemical medicine in the production to reach the standard and lower the costs. In conclusion, the peak area ratio of chiral isomers could be taken as a key quality index.
危险品化学品经营许可证（带存储）