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 method was developed for the simultaneous determination of losartan and its major active metabolite, EXP-3174, in human plasma. The two analytes and the internal standard (DuP-167) were extracted from plasma under acidic conditions by using solid-phase extraction cartridges containing a sorbent of copolymer, poly(divinylbenzene-co-N-vinylpyrrolidone). The analytes were separated by LC equipped with a reversed-phase C18 column, and introduced into the mass spectrometer via the electrospray ion source with pneumatically-assisted nebulization. For LC-MS-MS samples, an isocratic mobile phase consisting of [0.1% triethylamine-0.1% acetic acid (pH 7.1)]-acetonitorile (65:35, v/v) was used, and the assay was monitored for the negative fragment ions of the analytes. The method demonstrated linearity from 1 to 1000 ng/ml for both losartan and EXP-3174. The limit of quantification for both compounds in plasma was 1 ng/ml. This assay method may be useful for the measurement of levels of the two compounds in clinical studies of losartan.
Iwasa
T
T
Drug Metabolism, Development Research Laboratories, Banyu Pharmaceutical Co., Ltd., Osato-gun, Saitama, Japan.
Takano
T
T
Hara
K
K
Kamei
T
T
D000959:Antihypertensive Agents / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D006801:Humans; D007093:Imidazoles / Q000097:blood*; D019808:Losartan / Q000097:blood*; D013058:Mass Spectrometry / Q000379:methods*; D011786:Quality Control; D012680:Sensitivity and Specificity; D013777:Tetrazoles / Q000097:blood*
D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; C066026:losartan carboxylic acid; D019808:Losartan