Simultaneous determination of a novel angiotensin II receptor blocking agent, losartan, and its metabolite in human plasma and urine by high-performance liquid chromatography.
A sensitive and selective high-performance liquid chromatographic method for the simultaneous determination of a new angiotensin II receptor blocking agent, losartan (DuP 753, MK-954, I), and its active metabolite, EXP3174 (II), in human plasma or urine is described. The two analytes and internal standard are extracted from plasma and urine at pH 2.5 by liquid-liquid extraction and analyzed on a cyano column with ultraviolet detection at 254 nm. The mobile phase is composed of acetonitrile and phosphate buffer at pH 2.5. The limit of quantification for both compounds in plasma is 5 ng/ml. The limit in urine is 20 and 10 ng/ml for I and II, respectively. The assay described has been successfully applied to samples from pharmacokinetic studies.
Furtek
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Department of Drug Metabolism, Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.
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D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds / Q000097:blood / Q000378:metabolism* / Q000652:urine; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007093:Imidazoles / Q000097:blood / Q000378:metabolism* / Q000652:urine; D019808:Losartan; D015203:Reproducibility of Results; D013056:Spectrophotometry, Ultraviolet; D013777:Tetrazoles / Q000097:blood / Q000378:metabolism* / Q000652:urine
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; C066026:losartan carboxylic acid; D019808:Losartan