Assay of TNP-470 and its two major metabolites in human plasma by high-performance liquid chromatography-mass spectrometry.
In this study, a sensitive, specific assay for the determination of TNP-470 and its two major metabolites M-IV (also know as AGM-1883) and M-II in human plasma is reported. The assay involves liquid-liquid extraction of acidified plasma followed by reversed-phase high-performance liquid chromatography-atmospheric pressure chemical ionization-tandem mass spectrometry. A liquid-liquid extraction using an organic solvent mixture (methyl-tert-butyl-ether-hexane, 1:1, v/v) is used in place of solid-phase extraction because it provides consistent recoveries for all analytes, including the internal standard. Retention times for the analytes and internal standard are less than 7 min. Within- and between-day precision is < or = 6.5% and < or = 13.3% relative standard deviation, respectively, for the three analytes. The lower limits of quantitation are 0.25, 0.5, and 1.0 ng/mL for TNP-470, M-IV, and M-II, respectively.
Whalen
Carl T
CT
Covance Laboratories Inc., Madison, WI 53704, USA.
Hanson
Glenn D
GD
Putzer
Kathy J
KJ
Mayer
Michael D
MD
Mulford
Darcy J
DJ
D000903:Antibiotics, Antineoplastic / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003510:Cyclohexanes; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods*; D000077609:O-(Chloroacetylcarbamoyl)fumagillol; D012015:Reference Standards; D012680:Sensitivity and Specificity; D012717:Sesquiterpenes / Q000097:blood*
D000903:Antibiotics, Antineoplastic; D003510:Cyclohexanes; D012717:Sesquiterpenes; D000077609:O-(Chloroacetylcarbamoyl)fumagillol