title: Characterization of metabolites of larotaxel in rat by liquid chromatography coupled with Q exactive high-resolution benchtop quadrupole orbitrap mass spectrometer.
abstract: 1. Liquid-chromatography (LC) high-resolution (HR) mass spectrometry (MS) analysis can record HR full scans for drug metabolism studies. Larotaxel is a taxane analog that has the potential for the treatment of various types of cancer. 2. In this study, the metabolism of larotaxel was evaluated after an intravenous dose of 8 mg/kg via the caudal vein to healthy rats and its metabolites were characterized by high performance liquid chromatography coupled with a Q Exactive high-resolution benchtop quadrupole orbitrap mass spectrometer. Rat bio-samples were separated on a Capcell Pak C18column (2.1 i.d. × 100 mm; 2.7 μm) with mobile phase of acetonitrile and water. 3. As a result, a total of 34 metabolites were detected and identified by comparing the molecular masses, retention times and spectral patterns of the analytes with those of the parent drug. Three metabolites were confirmed by comparison with reference substances. 4. The prominent metabolites were mainly hydroxyl, dihydroxyl, trihydroxyl and 10-desacetyl analogs of larotaxel, some of which resulted from oxidation of the tert-butyl groups on the side chain and further oxidation and cyclization of the tert-butyl hydroxylated metabolites.
authors.affiliation: a Department of Medical Function , School of Medicine, Yangtze University , Jingzhou , China and.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Liu
authors.affiliation: b Chromatography and Mass Spectrometry Division, Thermo Fisher Scientific , Shanghai , China.
authors.forename: Pengyi
authors.initials: P
authors.lastname: Hou
authors.affiliation: a Department of Medical Function , School of Medicine, Yangtze University , Jingzhou , China and.
authors.forename: Lian
authors.initials: L
authors.lastname: Liu
authors.affiliation: a Department of Medical Function , School of Medicine, Yangtze University , Jingzhou , China and.
authors.forename: Feng
authors.initials: F
authors.lastname: Qian
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005243:Feces; D013058:Mass Spectrometry / Q000379:methods*; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry / Q000379:methods; D043823:Taxoids / Q000378:metabolism* / Q000493:pharmacokinetics*; D014018:Tissue Distribution
chemical_list: D043823:Taxoids; C531079:larotaxel
keywords: Bio-samples; Q Exactive; larotaxel; metabolites