title: Simultaneous determination of Z-SU5416 and its interconvertible geometric E-isomer in rat plasma by LC/MS/MS.
abstract: SU5416 is a selective inhibitor of vascular endothelial growth factor (VEGF) receptor, which plays a major role in vascular angiogenesis. SU5416 exists as the thermodynamically stable and pharmacologically active cis isomer (Z-isomer) in the solid state. In light-exposed solutions the unstable trans isomer (E-isomer) is formed. The E-isomer is unstable for synthesis and isolation and the analytical standard of the E-isomer is unavailable. A new, simple, fast and reliable LC/MS/MS method was developed to quantify both isomers simultaneously in rat plasma samples in order to support the study of disposition kinetics of Z- and E-SU5416. This method is sensitive (LOQ = 0.5 ng/ml), reproducible, and has a wide linear range (0.5-2500 ng/ml).
authors.affiliation: Department of Bioanalysis, Metabolism and Phamacokinetics, SUGEN Inc., 230 E. Grand Ave., South San Francisco, CA 94080, USA.
authors.forename: Yeping
authors.initials: Y
authors.lastname: Zhao
authors.forename: Juthamas
authors.initials: J
authors.lastname: Sukbuntherng
authors.forename: Lida
authors.initials: L
authors.lastname: Antonian
mesh_terms: D000818:Animals; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D007211:Indoles / Q000097:blood*; D011758:Pyrroles / Q000097:blood*; D051381:Rats; D013237:Stereoisomerism; D013678:Technology, Pharmaceutical / Q000379:methods*
chemical_list: D007211:Indoles; D011758:Pyrroles; C116890:Semaxinib