title: Measurement of clomipramine, N-desmethyl-clomipramine, imipramine, and dehydroimipramine in biological fluids by selective ion monitoring, and pharmacokinetics of clomipramine.
abstract: To quantitatively determine tricyclic antidepressant agents, we used a combined gas chromatograph/mass spectrometer system, and deuterium-labeled internal standards. Recovery exceeds 95% and the coefficient of variation is less than 4% for human whole-blood samples supplemented with 5 to 15 ng of clomipramine hydrochloride or 20 to 60 ng of dehydroimipramine hydrogen fumarate per milliliter. For both amines, the detection limit is 0.3 mug/liter; Six healthy volunteers who received a single oral dose of 50 mg of clomipramine hydrochloride showed peak drug concentrations in the blood 3 to 5 h after administration, ranging between 14.4 and 30.1 mug/liter. Plasma/whole blood concentration ratios varied from 0.70 to 1.20, and the cumulative renal elimination from 0 to 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.
mesh_terms: D000928:Antidepressive Agents / Q000097:blood*; D002997:Clomipramine / Q000031:analogs & derivatives / Q000097:blood* / Q000138:chemical synthesis; D003984:Dibenzazepines / Q000097:blood*; D005069:Evaluation Studies as Topic; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D006801:Humans; D007099:Imipramine / Q000031:analogs & derivatives* / Q000097:blood*; D012044:Regression Analysis; D013997:Time Factors
chemical_list: D000928:Antidepressive Agents; D003984:Dibenzazepines; D002997:Clomipramine; D007099:Imipramine