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气相色谱-质谱联用法测定血浆中的三甲丙咪嗪及其去甲基化和羟基化代谢产物

Determination of trimipramine and its demethylated and hydroxylated metabolites in plasma by gas chromatography-mass spectrometry.

作者信息

Eap C B, Koeb L, Baumann P

机构信息

Unité de Biochimie et Psychopharmacologie Clinique, Départment Universitaire de Psychiatrie Adulte (DUPA), Prilly-Lausanne, Switzerland.

出版信息

J Chromatogr. 1994 Jan 14;652(1):97-103. doi: 10.1016/0378-4347(93)e0366-x.

Abstract

A gas chromatographic-mass spectrometric (GC-MS) method has been developed, for the determination of trimipramine (TRI), desmethyltrimipramine (DTRI), didesmethyltrimipramine (DDTRI), 2-hydroxytrimipramine (2-OH-TRI) and 2-hydroxydesmethyltrimipramine (2-OH-DTRI). The method includes two derivatization steps with trifluoroacetic acid anhydride and N-methyl-N-(tert.-butyldimethyl silyl)trifluoroacetamide and the use of an SE-54 capillary silica column. The limits of quantitation were found to be 2 ng/ml for DTRI and 4 ng/ml for all other substances. Besides, methods have been optimized for the hydrolysis of the glucuronic acid conjugated metabolites. This specific detection method is useful, as polymedication is a usual practice in clinical situations, and its sensitivity allows its use for single-dose pharmacokinetic studies.

摘要

已开发出一种气相色谱 - 质谱联用(GC-MS)方法,用于测定三甲丙咪嗪(TRI)、去甲基三甲丙咪嗪(DTRI)、双去甲基三甲丙咪嗪(DDTRI)、2-羟基三甲丙咪嗪(2-OH-TRI)和2-羟基去甲基三甲丙咪嗪(2-OH-DTRI)。该方法包括用三氟乙酸酐和N-甲基-N-(叔丁基二甲基甲硅烷基)三氟乙酰胺进行两步衍生化步骤,并使用SE-54毛细管硅胶柱。发现DTRI的定量限为2 ng/ml,其他所有物质的定量限为4 ng/ml。此外,已针对葡萄糖醛酸结合代谢物的水解对方法进行了优化。这种特定的检测方法很有用,因为在临床情况下联合用药很常见,其灵敏度使其可用于单剂量药代动力学研究。

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