Relevant Financial Disclosures
(within past 24 months)
No relevant financial relationship(s) to disclose.
Abstract
Introduction: Venetoclax, a BCL-2-inhibitor for the treatment of B-cell lymphoma associated with chromosome 17p deletion, is used more and more in the clinics. Because of severe toxicity, venetoclax has to be titrated at the beginning of the therapy. Further, it is metabolized over CYP3A4 and therefore prone to interactions, which makes therapeutic drug monitoring highly recommended.
Objectives: We aimed to develop a fast, simple and sensitive high-throughput LC-MS/MS method for the analysis of venetoclax in clinical routine.
Methods: 50 µL of plasma were mixed with the precipitation solution including the internal standard (d7-venetoclax) and centrifuged afterwards. The supernatant was transferred into autosampler vials and 20 µL was injected into the LC system using reversed phase chromatography with isocratic conditions. Detection was done by electrospray ionization mass spectrometry in the positive ionization mode. The method has been fully validated according to EMA and US-FDA guidelines.
Results: The method was shown to be linear over the entire calibration range (0.01-5.0 mg/L) with a lower limit of quantification at 0.01 mg/L. For within-day and between-day analysis, the CV's were <4.8% and the accuracy was between 95-98%. The method was demonstrated to be free of matrix effects for serum, heparin-, and EDTA-plasma.
Conclusion: The presented LC-MS/MS method allows a fast, simple and reliable determination of venetoclax.
= Discovery stage.
= Translation stage.
= Clinically available.
