Method for the simultaneous determination of losartan and its major metabolite, EXP-3174, in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry

A liquid chromatography-electrospray ionization tandem mass spectrometric m ethod was developed for the simultaneous determination of losartan and its major active metabolite, EXP-3174, in human plasma. The two analytes and th e internal standard (DuP-167) were extracted from plasma under acidic condi tions by using solid-phase extraction cartridges containing a sorbent of co polymer, poly(divinylbenzene-co-N-vinylpyrrolidone). The analytes were sepa rated by LC equipped with a reversed-phase C-18 column, and introduced into the mass spectrometer via the electrospray ion source with pneumatically-a ssisted nebulization. For LC-MS-MS samples, an isocratic mobile phase consi sting of [0.1% triethylamine-0.1% acetic acid (pH 7.1)]-acetonitorile (65:3 5, v/v) was used, and the assay was monitored for the negative fragment ion s of the analytes. The method demonstrated linearity from 1 to 1000 ng/ml f or both losartan and EXP-3174. The Limit of quantification for both compoun ds in plasma was 1 ng/ml. This assay method may be useful for the measureme nt of levels of the two compounds in clinical studies of losartan. (C) 1999 Elsevier Science B.V. All rights reserved.