LC/MS/MS determination of omapatrilat, a sulfhydryl-containing vasopeptidase inhibitor, and its sulfhydryl- and thioether-containing metabolites in human plasma

被引：24

作者：

Jemal, M ^{[1
]}

Khan, S ^{[1
]}

Teitz, DS ^{[1
]}

McCafferty, JA ^{[1
]}

Hawthorne, DJ ^{[1
]}

机构：

[1] Bristol Myers Squibb Co, Pharmaceut Res Inst, Bioanalyt Res, Clin Discovery, New Brunswick, NJ 08903 USA

来源：

ANALYTICAL CHEMISTRY | 2001年 / 73卷 / 22期

关键词：

D O I：

10.1021/ac010532d

中图分类号：

O65 [分析化学];

学科分类号：

070302 ; 081704 ;

摘要：

Omapatrilat, the most clinically advanced member of a new class of cardiovascular agents, vasopeptidase inhibitors, is under development at Bristol-Myers Squibb Pharmaceutical Research Institute for the treatment of hypertension and heart failure. An electrospray LC/MS/MS method has been developed and validated for the simultaneous determination of omapatrilat and its four metabolites in human plasma. Since omapatrilat and two of the metabolites are sulfhydryl-containing compounds, methyl acrylate was used to stabilize these compounds in human blood and plasma samples. Methyl acrylate reacted instantly with the sulfhydryl group to form a derivative that was stable in blood and plasma. Extraction of the analytes from plasma samples was achieved by semiautomated liquid-liquid extraction, where a robotic liquid handler performed the liquid-transferring steps. The mass spectrometer Was operated in the negative ion selected-reaction-monitoring mode. The calibration curve ranges were 0.5-250 ng/mL for omapatrilat and one metabolite and 2.0-250 ng/mL for the other three metabolites.

引用

页码：5450 / 5456

页数：7

共 13 条

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