【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０μｇ／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０μｇ／ｍｌ，定量限是５０μｇ／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更多还原

【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.更多还原