GLC–mass spectrometric determination of maprotiline and its major metabolite using stable isotope-labeled analog as internal standard

Abstract

A quantitative GLC–mass spectrometric assay was developed for the determination of maprotiline and its major metabolite, desmethylmaprotiline, in animal and human plasma. The assay utilizes selective-ion focusing to monitor, in a GLC effluent, the fragment ions and the base peaks of maprotiline and desmethylmaprotiline trifluo-roacetamides generated by electron-impact ionization. Maprotiline-d3 was the internal standard. The assay can measure 2ng of maprotiline (and the metabolite)/ml of plasma with ∼5% precision. The curves relating the amounts of maprotiline and the metabolite added versus the amounts experimentally found over a large concentration range were linear with nearly zero intercepts and slopes of 0.99 ± 0.01 and 0.98 ± 0.02, respectively. The method was used to study the pharmacokinetic pattern of the drug in rabbits as well as to analyze intact maprotiline and the metabolite in patients maintained on therapeutic doses of maprotiline. Assay specificity was confirmed by complete consistency of the mass spectra of maprotiline and desmethylmaprotiline with those of the authentic materials.