Simultaneous determination of tropatepine and its major metabolites by high-performance liquid chromatographic-mass spectrometric identification. Application to metabolic and kinetic studies.
Tropatepine is used to combat against extrapyramidal syndrome induced by neuroleptic drugs. A high-performance liquid chromatographic method was proposed for the simultaneous determination of tropatepine and its potential metabolites in biological fluids. After double extraction of compounds in hexane and back-extraction in hydrochloric acid, the chromatographic separation was performed on a reversed-phase column with an acetonitrile--perchlorate buffer mixture as mobile phase. Compounds were detected at 229 nm and the detection limit was about 15 ng/ml. The method was applied to bile and urine samples collected in rats, after a single high oral dose of 100 mg/kg of tropatepine hydrochloride. Gas chromatography-mass spectrometry was used for identification of the potential metabolites. Nortropatepine and tropatepine S-oxide were identified in this way, and it seemed that tropatepine was subjected to a large and intense metabolic process. The analytical procedure and the results of the metabolic investigation were applied to a preliminary pharmacokinetic study in patients undergoing long-term oral therapy with tropatepine.
D000818:Animals; D001646:Bile / Q000032:analysis; D002851:Chromatography, High Pressure Liquid; D003988:Dibenzothiepins / Q000032:analysis* / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D007202:Indicators and Reagents; D007700:Kinetics; D008297:Male; D010276:Parasympatholytics / Q000032:analysis* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013056:Spectrophotometry, Ultraviolet
D003988:Dibenzothiepins; D007202:Indicators and Reagents; D010276:Parasympatholytics; C013322:tropatepine