A bioanalytical method development and validation of leniolisib by reverse phase high-performance liquid chromatography in rat plasma and its application in pharmacokinetic studies

Abstract

Background

An oral selective phosphoinositide 3-kinase (PI3K) delta inhibitor, leniolisib, is currently being developed by Pharming Group NV. The drug has been in-licensed by Novartis to treat immunodeficiency diseases. This work aimed to create and verify a rapid and simple high-performance liquid chromatography technique for quantifying leniolisib in rat plasma. Sorafenib was utilized as the internal standard.

Results

A bioanalytical method was established for analyzing rat plasma using an Inertsil ODS-4 C₁₈ column with dimensions of 150 mm length, 4.6 mm internal diameter, 3.0 µm particle size and 10 nm pore size. The mobile phase was a mixture of acetonitrile and phosphate buffer with a pH of 7.4 in a 40:60 proportion. The flow rate was set at 1 ml/min, and the analyte was detected using PDA detection at a wavelength of 294 nm. A linear calibration curve consisting of seven points was produced within the concentration range of leniolisib in plasma, ranging from 150 to 6000 ng/ml. The accuracy ranged from 89.82 to 91.69%, and %CV was less than 6%. Further investigation of the pharmacokinetics of leniolisib in the oral solution at 10 mg/kg was carried out using the method that had been devised.

Conclusion

The proposed methodology is appropriate for the routine analysis of leniolisib in plasma samples, which is crucial for facilitating research on the drug's bioavailability and bioequivalence.