title: LC/MS/MS determination of omapatrilat, a sulfhydryl-containing vasopeptidase inhibitor, and its sulfhydryl- and thioether-containing metabolites in human plasma.
abstract: 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.
authors.affiliation: Bioanalytical Research, Clinical Discovery, Bristol-Myers Squibb Pharmaceutical Research Institute, New Brunswick, New Jersey 08903-0191, USA. mohammed.jemal@bms.com
authors.forename: M
authors.initials: M
authors.lastname: Jemal
authors.forename: S
authors.initials: S
authors.lastname: Khan
authors.forename: D S
authors.initials: DS
authors.lastname: Teitz
authors.forename: J A
authors.initials: JA
authors.lastname: McCafferty
authors.forename: D J
authors.initials: DJ
authors.lastname: Hawthorne
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D015394:Molecular Structure; D011725:Pyridines / Q000097:blood*; D013048:Specimen Handling; D021241:Spectrometry, Mass, Electrospray Ionization; D013438:Sulfhydryl Compounds / Q000097:blood / Q000737:chemistry; D013440:Sulfides / Q000097:blood / Q000737:chemistry; D013841:Thiazepines / Q000097:blood*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D011725:Pyridines; D013438:Sulfhydryl Compounds; D013440:Sulfides; D013841:Thiazepines; C106266:omapatrilat