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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 C18 column (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.
Acknowledgements
This work was supported by Starting Grant of Yangtze University [grant no. 7012500735] and Yangtze Fund for Youth Teams of Science and Technology Innovation [grant no. 2016YZYT1128].
Declaration of interest
The authors report no conflicts of interest. The authors alone are responsible for the content and writing of this article.
This work was supported by Starting Grant of Yangtze University [grant no. 7012500735] and Yangtze Fund for Youth Teams of Science and Technology Innovation [grant no. 2016YZYT1128].