| Summary: | Venetoclax has emerged as a breakthrough for treatment of leukemia with a wide interindividual variability in pharmacokinetics. Herein, a rapid, sensitive, and reliable UPLC-MS/MS method for quantification of venetoclax in plasma was developed and validated. The method was operated in the multiple-reaction monitoring (MRM) mode to detect venetoclax at m/z transition 868.5 > 321.0 and IS at 875.5 > 321.0, respectively. Protein precipitation prior to injection into the LC-MS/MS and the analyte was separated on an ACQUITY UPLC BEH C18 column by gradient elution with acetonitrile and 0.1% formic acid in water. Linear calibration curves were obtained in the range of 25–8000 ng/mL. The specificity, recovery, matrix effect, and stability also met the acceptance criteria of FDA guidance. The method was successfully applied to analyze plasma in acute myeloid leukemia (AML) patients. The peak plasma concentration (C<sub>max</sub>) of venetoclax in Chinese AML patient was 2966.0 ± 1595.0 ng/mL while the trough concentration (C<sub>min</sub>) was 1018.0 ± 729.4 ng/mL. Additionally, C<sub>max</sub> and C<sub>min</sub> showed a positive correlation with AST levels. Furthermore, C<sub>max</sub> was significantly higher in the older patients. The present method can be applied for TDM of venetoclax in treatment of hematological cancers.
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