title: Determination of angiotensin II receptor antagonist (E4177) in human plasma and urine by high-performance liquid chromatography.
abstract: A sensitive reversed-phase high-performance liquid chromatographic (HPLC) method with fluorescence detection was developed for the analysis of a new angiotensin II receptor antagonist, E4177, in human plasma and urine. The analyte and internal standard (I.S.) are extracted from acidified plasma and urine by liquid-liquid extraction and then refined by solid-phase extraction. The extraction recovery was greater than 90%. E4177 and I.S. were separated from endogenous components in plasma and urine on a C18 column using a mobile phase of acetonitrile-water-85% phosphoric acid (27.3:72.0:0.7, v/v). The eluent was monitored by fluorescence with excitation and emission set at 280 and 380 nm, respectively. The assay was linear from 2.5 to 1000 ng/ml of plasma and from 5 to 1500 ng/ml of urine. The limit of quantification was 2.5 and 5 ng/ml for plasma and urine, respectively. Inter- and intra-day coefficients of variation for the plasma and urine ranged from 0.6 to 4.7%. E4177 was stable in plasma and urine for at least 9 months during storage at -20 degrees C, respectively. The method was successfully applied to the determination of E4177 in plasma and urine for a pharmacokinetic study.
authors.affiliation: Department of Applied Drug Research, Eisai Co., Ltd., Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Seki
authors.forename: K
authors.initials: K
authors.lastname: Yamazaki
authors.forename: M
authors.initials: M
authors.lastname: Kayano
mesh_terms: D000284:Administration, Oral; D057911:Angiotensin Receptor Antagonists; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002940:Circadian Rhythm; D004355:Drug Stability; D005615:Freezing; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics; D016014:Linear Models; D011725:Pyridines / Q000008:administration & dosage / Q000032:analysis* / Q000737:chemistry / Q000493:pharmacokinetics; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013050:Spectrometry, Fluorescence; D013997:Time Factors
chemical_list: D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011725:Pyridines; C083778:3-((2'-carboxybiphenyl-4-yl)methyl)-2-cyclopropyl-7-methyl-3H-imidazo(4,5-b)pyridine