The metabolism of YiGan San and subsequent pharmacokinetic evaluation of four metabolites in rat based on liquid chromatography with tandem mass spectrometry
The metabolism of YiGan San and subsequent pharmacokinetic evaluation of four metabolites in rat based on liquid chromatography with tandem mass spectrometry
复制标题
基于液相色谱-串联质谱法的益肝散代谢及四种代谢物在大鼠体内的药代动力学评价
DOI：
10.1016/j.jchromb.2014.09.033
复制
发表时间：
2014-12-01
影响因子：
3
通讯作者：
Xie, Ning
中科院分区：
文献类型：
--
作者：
Gai, Yanan;Chen, Han;Xie, Ning
A new method based on liquid chromatography-tandem time-of-flight mass spectrometry was developed to identify the metabolites in rat urine after oral administration of YiGan San (YGS). Eighteen prototype compounds and four metabolites named 11-hydroxyhirsuteine, 19-carbonylhirsutine, 19-carbonyl-dihydrocorynantheine, and 18-hydroxy-geissoschizine methyl ether were identified. Subsequently, a method of high-performance liquid chromatography coupled with triple-quadrupole mass spectrometry was established for pharmacokinetic study of YGS in rat plasma. The concentration-time curves of four prototype compounds, senkyunolide I, ajmalicine, isocorynoxeine and rhynchophylline were constructed after an oral (9.1 g YGS per kilogram of body weight) administration in rats. Method validation revealed excellent linearity over the range 220.00-0.55, 220.00-0.55, 21.40-0.05, and 19.80-0.05 ng/mL for the four prototype compounds respectively. The stabilities results indicate that all of the analytes were stable in rat plasma in the autosampler for 24 h, under freeze/thaw cycles (4 times in 24 h), and at 20 degrees C for one week. Residual analysis, heteroskedasticity test, and goodness-of-fit test were also performed to determine the accuracy of the linear regression method. The pharmacokinetic parameters were obtained. Four hours after administration, compound 11-hydroxyhirsuteine can be detected in rat plasma. Compared with purified ligustilide, YGS required a slightly longer period to reach maximum concentration (C-max) in rat plasma. (C) 2014 Elsevier B.V. All rights reserved.
