Simultaneous determination of the pharmacokinetics of the active components of San-Chen-pill by UPLC-Q-Exactive-MS

UPLC-Q-Exactive-MS同时测定三臣丸中六种活性成分的药代动力学研究（英文）

In the present study, we developed a rapid, sensitive and efficient ultra high-performance liquid chromatography-tandem mass spectrometric(UPLC-Q-Exactive-MS) method, and six bioactive constituents in San-Chen-pill(SCP), including cholic acid(CA), hyodeoxycholic acid(HDCA), hydroxysafflor yellow A(HSYA), kaempferol-3-O-rutinoside(KFR), anhydrosafflor yellow B(AHSYB) and syringin(SRG), in rat plasma after oral administration of San-Chen-pill, were simultaneously determined. Plasma samples were pretreated with methanol for protein precipitation. Chromatography separation was performed on a SHIMADZU of shim-pack GIST C18 column using a gradient mobile phase consisting of acetonitrile and 0.1% formic acid aqueous solution. A tandem mass spectrometric detection with an electrospray ion source(HESI) interface was conducted in negative ionization mode. For all the six analytes of interest, the calibration curves were linear within the concentration rage of 0.50–1280 ng/m L with r≥0.99. The intra-day and inter-day precisions(in terms of relative standard deviation, RSD) were all below 12.7% for all six analytes. Extraction recovery, matrix effect and stability data all met the acceptance criteria of FDA guideline for bioanalytical method validation. In addition, San-Chen-pill is a traditional Mongolian herbal medicine that has been prepared with three medicinal herbs, Calculus bovis, Carthamus tinctorius L. and Concretio silicea bambusae, and it shows potent anti-anginal activity in all preparations with in a ratio of 1:1:1. The pharmacokinetic parameters of San-Chen-pill were reported herein for the first time, and this developed method was successfully used in a pharmacokinetic study for San-Chen-pill.

建立三臣丸药代动力学的UPLC-Q-Exactive-MS检测方法,同时测定大鼠血浆中胆酸、猪胆酸、羟基红花黄色素A、山奈酚-3-O-芸香糖苷、脱水红花黄色素B和紫丁香苷6种活性成分的含量。HPLC分离采用SHIMADZU GIST C18色谱柱,流动相为乙腈–0.1%甲酸溶液梯度洗脱。质谱检测采用HESI离子源负离子检测模式。6种活性成分的线性范围0.50–1280 ng/m L,r均大于0.99;日内及日间精密度(RSD)均小于12.7%;提取回收率、基质效应和稳定性的计算值均符合FDA生物分析方法验证准则。该文中的三臣丸为传统的蒙药复方,由牛黄、红花和天竺黄三味药材等量组成。该方法为首次报道,并且已成功应用于三臣丸的药代动力学研究。