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 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.
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Unité de Biochimie et Psychopharmacologie Clinique, Départment Universitaire de Psychiatrie Adulte (DUPA), Prilly-Lausanne, Switzerland.
Koeb
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Baumann
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D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003640:Dealkylation; D008401:Gas Chromatography-Mass Spectrometry; D005965:Glucuronates / Q000378:metabolism; D006801:Humans; D006900:Hydroxylation; D014299:Trimipramine / Q000097:blood* / Q000493:pharmacokinetics
D005965:Glucuronates; D014299:Trimipramine