DETERMINATION OF TRIMIPRAMINE AND ITS DEMETHYLATED AND HYDROXYLATED METABOLITES IN PLASMA BY GAS-CHROMATOGRAPHY MASS-SPECTROMETRY

A gas chromatographic-mass spectrometric (GC-MS) method has been devel oped, for the determination of trimipramine (TRI), desmethyltrimiprami ne (DTRI), didesmethyltrimipramine (DDTRI), 2-hydroxytrimipramine (2-O H-TRI) and 2-hydroxydesmethyltrimipramine (2-OH-DTRI). The method incl udes two derivatization steps with trifluoroacetic acid anhydride and N-methyl-N-(tert.-butyldimethyl silyl)trifluoroacetamide and the use o f an SE-54 capillary silica column. The limits of quantitation were fo und to be 2 ng/ml for DTRI and 4 ng/ml for all other substances. Besid es, methods have been optimized for the hydrolysis of the glucuronic a cid 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.