In vitro and in vivo metabolic investigation of the Palbociclib by UHPLC-Q-TOF/MS/MS and in silico toxicity studies of its metabolites

Journal of Pharmaceutical and Biomedical Analysis
Balasaheb B ChavanM V N Kumar Talluri

Abstract

Palbociclib (PAB) is a CDK4/6 inhibitor and U. S Food and Drug Administration (FDA) granted regular approval for the treatment of hormone receptor (HR) positive, metastatic breast cancer in combination with an aromatase inhibitor in postmenopausal women. Metabolite identification is a crucial aspect during drug discovery and development as the drug metabolites may be pharmacologically active or possess toxicological activity. As there are no reports on the metabolism studies of the PAB, the present study focused on investigation of the in vitro and in vivo metabolic fate of the drug. The in vitro metabolism studies were carried out by using microsomes (HLM and RLM) and S9 fractions (Human and rat). The in vivo metabolism of the drug was studied by administration of the PAB orally to the Sprague-Dawley rats followed by analysis of urine, faeces and plasma samples. The sample preparation includes simple protein precipitation (PP) followed by solid phase extraction (SPE). The extracted samples were analyzed by ultrahigh-performance liquid chromatography-quadruple time-of-flight tandem mass spectrometry (UHPLC/Q-TOF/MS/MS). A total of 14 metabolites were detected in in vivo matrices. The PAB was metabolized via hydroxylation, oxida...Continue Reading

Citations

Jan 24, 2020·The Analyst·Marco Beccaria, Deirdre Cabooter
Nov 5, 2019·Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences·Julia JoliboisBernard Royer
Oct 27, 2021·Bioanalysis·Gangireddy Navitha ReddyRajesh Sonti
Nov 24, 2020·Breast Care·Eudald FelipVanesa Quiroga

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