Measurement of clomipramine, N-desmethyl-clomipramine, imipramine, and dehydroimipramine in biological fluids by selective ion monitoring, and pharmacokinetics of clomipramine
Dubois, J.P.; Küng, W.; Theobald, W.; Wirz, B.
Clinical Chemistry 22(6): 892-897
1976
ISSN/ISBN: 0009-9147 PMID: 1277478 Document Number: 103291
To quantitatively determine tricyclic antidepressant agents, a combined gas chromatograph/mass spectrometer system and deuterium-labeled internal standards were used. Recovery exceeds 95%, and the coefficient of variation is less than 4% for human whole-blood samples supplemented with 5-15 ng of clomipramine hydrochloride or 20-60 ng of dehydroimipramine hydrogen fumarate per ml. For both amines the detection limit is 0.3 .mu.g/l. Six healthy volunteers who received a single oral dose of 50 mg of clomipramine hydrochloride showed peak drug concentrations in the blood 3-5 h after administration, ranging between 14.4-30.1 .mu.g/l. Plasma/whole blood concentration ratios varied from 0.70-1.20, and the cumulative renal elimination from 0-72 h is less than 0.2% of the dose. This method is suitable for in vivo bioavailability studies of unchanged clomipramine, dehydroimipramine and imipramine after a single oral dose of as little as 25 mg.