title: Simultaneous determination of losartan and EXP3174 in human plasma and urine utilizing liquid chromatography/tandem mass spectrometry.
abstract: Losartan is an orally active angiotensin II receptor antagonist indicated for the treatment of hypertension. EXP3174 is an active metabolite, which contributes to the overall activity of losartan. Analytical methods for the simultaneous determination of losartan and its active metabolite EXP3174 in human plasma and urine with limited plasma sample size have been developed and validated to support a pediatric clinical program. In both methods, analytes are extracted from the matrixes by liquid-liquid extraction and separated using reverse phase high-performance liquid chromatography (HPLC). A tandem mass spectrometer (MS/MS) with a Turbo ionspray (TIS) interface in multiple-reaction-monitoring (MRM) mode is used for detection of the analytes in both methods. The plasma method has a lower limit of quantitation (LOQ) of 1 ng/ml with a linearity range of 1-500 ng/ml for losartan and EXP3174 using 100 microl of plasma. For the urine method, the LOQ for both losartan and EXP3174 is 2 ng/ml using 0.5 ml of urine, and the linearity range for both analytes is 2-1000 ng/ml. Validation procedures have proven that both methods are robust, accurate, and reproducible. Both methods have been used to assay clinical samples and provided satisfactory results.
authors.affiliation: Department of Drug Metabolism, Merck Research Laboratories, WP 75A-303, West Point, PA 19486, USA. michelle.polinko@merck.com
authors.forename: Michelle
authors.initials: M
authors.lastname: Polinko
authors.forename: Kerry
authors.initials: K
authors.lastname: Riffel
authors.forename: Hengchang
authors.initials: H
authors.lastname: Song
authors.forename: Man-Wai
authors.initials: MW
authors.lastname: Lo
mesh_terms: D000959:Antihypertensive Agents / Q000032:analysis* / Q000097:blood / Q000652:urine; D002675:Child, Preschool; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D007093:Imidazoles / Q000032:analysis* / Q000097:blood / Q000652:urine; D007202:Indicators and Reagents; D019808:Losartan / Q000032:analysis* / Q000097:blood / Q000652:urine; D013058:Mass Spectrometry; D011786:Quality Control; D012015:Reference Standards; D015203:Reproducibility of Results; D013777:Tetrazoles / Q000032:analysis* / Q000097:blood / Q000652:urine
chemical_list: D000959:Antihypertensive Agents; D007093:Imidazoles; D007202:Indicators and Reagents; D013777:Tetrazoles; C066026:losartan carboxylic acid; D019808:Losartan