Gas chromatographic quantitation of methoxyphenamine and three of its metabolites in plasma.
Sensitive gas chromatographic procedures for the determination of methoxyphenamine and three of its metabolites in plasma have been developed. The metabolites were measured using an electron-capture detector. This simple procedure is based on the precipitation of protein from a 1-ml plasma sample with 10% trichloroacetic acid, followed by aqueous derivatization with pentafluorobenzoyl chloride at pH 9.2 and a single-step cyclohexane extraction. The lower limit of detection for the N-desmethyl, O-desmethyl and aromatic 5-hydroxy metabolites of methoxyphenamine were 1.6, 3.1 and 2.2 ng ml-1, respectively, with coefficients of variation less than 10%. The poor electron-capture response of fluorinated derivatives of methoxyphenamine necessitated the use of nitrogen-phosphorus detection. Extractive derivatization with pentafluorobenzoyl chloride, without the need for protein precipitation, enabled quantitation of methoxyphenamine down to 3.8 ng ml-1 from a 2-ml aliquot of plasma. In a pilot study involving healthy volunteers who received a single oral dose of methoxyphenamine hydrochloride plasma concentration could be followed in all three subjects for at least 24, 32, 12 and 4 h for methoxyphenamine and the O-desmethyl, 5-hydroxy and N-desmethyl metabolites, respectively.
D000318:Adrenergic beta-Agonists / Q000097:blood*; D000661:Amphetamine / Q000097:blood; D000662:Amphetamines; D055598:Chemical Phenomena; D002621:Chemistry; D002849:Chromatography, Gas / Q000379:methods; D006801:Humans; D007700:Kinetics; D008297:Male; D008694:Methamphetamine / Q000031:analogs & derivatives* / Q000097:blood; D013696:Temperature
D000318:Adrenergic beta-Agonists; D000662:Amphetamines; C043935:N-desmethylmethoxyphenamine; D008694:Methamphetamine; C043936:O-desmethylmethoxyphenamine; C043934:5-hydroxymethoxyphenamine; D000661:Amphetamine; C005157:methoxyphenamine