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.

Venetoclax dose adjustment due to drug-drug interactions: a case report and literature review

“…Presently, research on monitoring serum Venetoclax concentration during treatment is still less. To our knowledge, there are only two methodological studies published [ 29 , 30 ], and no clinical intervention study is performed to prove the effect of serum drug concentration on treatment safety. Both the two existing studies reported that the steady-state trough concentration of Venetoclax during treatment in AML patients fluctuated in a range of 250–8000 ng/ml.…”

Pharmacokinetic analysis of crushed venetoclax tablets combined with azacitizine for recurrent pediatric acute myeloid leukemia (AML)

“…Blood samples were collected before and six hours after VEN administration, and the minimum (C min ) and maximum plasma concentrations (C max ) were measured. The VEN concentration in the patients' plasma was measured using highperformance liquid chromatography-ultraviolet 4 .…”

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

“…Although these methods had a relatively low quantitative lower limit, analytical run-time was longer and larger plasma sample sizes are not suitable for paediatric samples. In the published literature, either the lower limit of quantification was high or the analysis time was too long [11,12]. Compared with these methods, our method only needed 50 μL plasma samples, the analysis time was 5 min, and the lower limit of quantification was 10 μL mL À1 .…”