Simultaneous determination of venetoclax and obinutuzumab by LC-MS/MS and its application to pharmacokinetic drug interaction studies
DOI:
https://doi.org/10.1590/s2175-97902026e24723Keywords:
Venetoclax, Obinutuzumab, Gossypol, Rat plasma, PharmacokineticsAbstract
A novel LC-MS/MS method was developed and validated for the simultaneous quantification of venetoclax and obinutuzumab in rat plasma and successfully applied to pharmacokinetic investigations in male wistar rats. Chromatography was performed on a Symmetry C18 column (150 x 4.6 mm, 3.5 µm) column utilizing multiple-reaction monitoring (MRM) mode to evaluate venetoclax, obinutuzumab, and the internal standard gossypol, following which they were extracted using liquid-liquid extraction. The assay demonstrated high sensitivity, excellent reproducibility, and full compliance with FDA bioanalytical validation criteria, with venetoclax exhibiting a linear range of 25–200 ng/mL and obinutuzumab 6.25–50 ng/mL, respectively. The high-abundant mass transitions were seen starting from 869.4425 and 603.8597 m/z for venetoclax and 146.5948 and 67.6239 m/z for obinutuzumab and Gossypol (IS) 519.5638 and 206.7486 m/z, respectively. Upon application, the study successfully characterized the pharmacokinetic profiles of venetoclax and obinutuzumab in Wistar rats, revealing differences in absorption and systemic exposure between the two compounds. Venetoclax demonstrated a higher Cmax and AUC with a delayed Tmax compared to obinutuzumab, although both shared a similar elimination half-life of 20 hours. The results indicate consistent and stable pharmacokinetic behaviour under the tested conditions, supporting future therapeutic drug monitoring and preclinical drug development.
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The data supporting the conclusions of this study are available from the corresponding author upon reasonable request, subject to ethical considerations and data sharing agreements.
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