Rapidly determine venetoclax in plasma sample using an LC-MS/MS method and apply it in TDM for acute leukemia children patient

Venetoclax is the first oral Bcl-2 inhibitor with high affinity targeting tumor cell apoptosis mechanism. In this study we developed a simple, sensitive and reliable LC–MS/MS method to determine venetoclax in children's hemolytic or lipemic samples. The method utilized an electrospray ion source and operated in multiple reaction monitoring mode. Venetoclax-d8 was used as an internal standard. Plasma samples were precipitated by acetonitrile containing 10% dimethyl sulfoxide and were separated by a Hypersil GOLD column (2.1 mm × 150 mm, 5 μm). The mobile phase consisted of acetonitrile-2 mM ammonium acetate (30:70, v/v) containing 0.4% formic acid. The quantification for venetoclax and venetoclax-d8 were m/z 868.1 → 636.1, m/z 876.1 → 644.1, respectively. The linear range was 10–2,000 ng mL−1 for venetoclax. The matrix in normal plasma, hemolytic or lipemic plasma had no significant effect on the detection results. The specificity, recovery and stability also met the acceptance criteria of guiding principles for the validation of biological sample quantitative analysis presented in the Chinese Pharmacopoeia (2015). As a result, this method is particularly suitable for determining venetoclax in hemolytic or lipemic samples from children with acute myeloid leukemia. The method, with the application of monitoring drug concentrations in pediatric patients, was successful.