Determination of Venetoclax Concentration in Plasma Using High-Performance Liquid Chromatography.

ABSTRACT

Venetoclax is an oral B-cell lymphoma-2 protein inhibitor. It is a key drug for the treatment of chronic lymphocytic leukemia and acute myeloid leukemia. However, venetoclax is administered at a fixed dose, irrespective of body surface area or weight. Furthermore, the plasma concentration of venetoclax varies widely between individuals and is influenced by diet. Therefore, individualized dosing using therapeutic drug monitoring (TDM) may help to optimize treatment in clinical practice. In this study, we aimed to develop a simple method to determine venetoclax concentrations in plasma. The analysis required the extraction of a 50-µL plasma sample and precipitation of proteins using acetonitrile extraction. Venetoclax and the internal standard (12.5-µg/mL ibrutinib) were separated by high-performance liquid chromatography (HPLC). The calibration curve was linear over the plasma venetoclax concentration range 0.25-10 µg/mL with a coefficient of determination (r2) of 0.9999. The coefficients of intra-day and inter-day validation were 0.8-4.1% and 1.3-3.3%, respectively. The assay accuracy was -2.8 to 1.6%, and the recovery was >97.2%. These results demonstrate a very simple, novel and sensitive HPLC-UV-based method for determining the concentration of plasma venetoclax, and confirm its applicability to the TDM of venetoclax in a clinical setting.