HPLC assays to simultaneously determine the angiotensin-AT1 antagonist losartan as well as its main and active metabolite EXP3174 in biological material of humans and rats

被引:62
作者
Soldner, A
Spahn-Langguth, H
Mutschler, E
机构
[1] Univ Frankfurt, Bioctr Niederursel, Dept Pharmacol, D-60439 Frankfurt, Germany
[2] Univ Halle Wittenberg, Dept Pharmaceut Chem, D-06120 Halle, Germany
关键词
losartan; EXP; 3174; nonpeptide Angiotensin-AT(1) antagonists; reversed-phase high-performance liquid chromatography; solid-phase extraction; plasma; urine; blood; bile; tissues; rats;
D O I
10.1016/S0731-7085(97)00128-3
中图分类号
O65 [分析化学];
学科分类号
070302 ; 081704 ;
摘要
Novel rapid and sensitive HPLC assays were developed to simultaneously determine losartan and its main active metabolite EXP 3174 in biological material of humans and rats following solid-phase or liquid-liquid extraction. The analytes were separated on a 3 mu m particle-sized ULTREMEX(TM) CN column, which was preceeded by a 5 mu m particle-sized guard column, using UV-detection at 245 nm. The assays provided high sensitivity with limits of quantification (LoQ) of 5 ng ml(-1) for both compounds in human and rat plasma and 10 ng ml(-1) in human and rat urine, respectively. In rat blood, bile and various tissues, limits of quantifications were achieved that ranged 10-15 ng per mi and per 100 mg tissue, respectively, for both analytes. (C) 1998 Elsevier Science B.V.
引用
收藏
页码:863 / 873
页数:11
相关论文
共 8 条
[1]   THE DISCOVERY OF DUP-753, A POTENT, ORALLY ACTIVE NONPEPTIDE ANGIOTENSIN-II RECEPTOR ANTAGONIST [J].
DUNCIA, JV ;
CARINI, DJ ;
CHIU, AT ;
JOHNSON, AL ;
PRICE, WA ;
WONG, PC ;
WEXLER, RR ;
TIMMERMANS, PBMWM .
MEDICINAL RESEARCH REVIEWS, 1992, 12 (02) :149-191
[2]  
DZAU VJ, 1988, CIRCULATION, V77, P4
[3]   SIMULTANEOUS DETERMINATION OF A NOVEL ANGIOTENSIN-II RECEPTOR BLOCKING-AGENT, LOSARTAN, AND ITS METABOLITE IN HUMAN PLASMA AND URINE BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY [J].
FURTEK, CI ;
LO, MW .
JOURNAL OF CHROMATOGRAPHY-BIOMEDICAL APPLICATIONS, 1992, 573 (02) :295-301
[4]  
SHAH VP, 1991, EUR J DRUG METAB PH, V16, P249
[5]  
STEARNS RA, 1992, DRUG METAB DISPOS, V20, P281
[6]  
STEARNS RA, 1995, DRUG METAB DISPOS, V23, P207
[7]  
TIMMERMANS PBMWM, 1993, PHARMACOL REV, V45, P205
[8]  
WONG PC, 1990, J PHARMACOL EXP THER, V255, P211