对映体选择性毛细血管相色谱测定微粒体中R-(-)-和S-(+)-美西律

对映体选择性毛细血管相色谱测定微粒体中R-(-)-和S-(+)-美西律

王似菊, 毛海琼, 曾苏^*

浙江医科大学药学院, 杭州 310031

收稿日期:1997-08-25 修回日期:1997-12-24 出版日期:1998-12-15 发布日期:1998-12-15
通讯作者: 曾苏*

Enantioselective Determination of R-(-)- and S-(+)-Mexiletine in Microsomal Incubates by Capillary gas Chromatography

Si-Ju Wang, Hai-Qiong Mao, Su Zeng^*

School of Pharmacy, Zhejiang Medical University, Hangzhou 310031

Received:1997-08-25 Revised:1997-12-24 Online:1998-12-15 Published:1998-12-15
Contact: Su Zeng*

摘要/Abstract

摘要： 本文建立了同时测定大鼠肝微粒体孵育液中R-(-)-和S-(+)-美西律的气相色谱/火焰离子化检测方法。首先,将美西律从微粒体孵育液中提取出来; 然后,与手性试剂S-(-)-N-三氟乙酰基脯氨酰氯反应形成酰胺类非对映体衍生物; 最后, 采用高分辨毛细管气相色谱分离测定。分析方法的线性范围为5.0~500.0 μg/ml; 平均回收率R-(-)-美西律是93.31%±5.59%, S-(+)-美西律是93.10%±5.11%(n = 10); 检测限是1.0 μg/ml, 定量限是5.0 μg/ml (RSD<16.5%)。该法已用于R-(-)-和S-(+)-美西律在大鼠肝微粒体中的氧化代谢研究。

关键词: 美西律, 毛细管气相色谱, 对映体分离

Abstract: A method for the assay of R-(-)- and S-(+)-mexiletine in rat liver microsomal incubates was developed. The method involved extraction of mexiletine from the microsomal incubates, and formation of mexiletine diastereomeric derivatives with a chiral reagent S-(-)-N-trifluoroacetyl prolyl chloride. Separation and quantitation of the diastereomeric mexiletine derivatives were carried out by a capillary gas chromatographic system with flame ionization detection. The assay was linear from 5 to 500 μg/ml for each enantiomer. The average recoveries of analytical method were 93.31%±5.59% and 93.10%±5.11% for R-(-)- and S-(+)-mexiletine, respectively. The limits of detection and quantitation for the method were 1.0 μg/ml and 5.0 μg/ml for the R-(-)- and S-(+)-mexiletine isomers, respectively. The reproducibility in the assay was better than 16.5% (RSD). The method has been applied to the metabolism study of R-(-)- and S-(+)-mexiletine in rat liver microsomal incubates.

Key words: Mexiletine, Capillary gas chromatography, Enantiomer separation

Supporting: The project was supported by the National Natural Science Foundation of China (# 39370850) and Zhejiang Provincial Natural Science Foundation (# 393031).

王似菊, 毛海琼, 曾苏^*. 对映体选择性毛细血管相色谱测定微粒体中R-(-)-和S-(+)-美西律[J]. .

Si-Ju Wang, Hai-Qiong Mao, Su Zeng^*. Enantioselective Determination of R-(-)- and S-(+)-Mexiletine in Microsomal Incubates by Capillary gas Chromatography[J]. .

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