Bioanalytical method development and validation for determination of olutasidenib and its application to pharmacokinetic studies

Abstract

Olutasidenib is an inhibitor licensed by the FDA, indicated against mutations in isocitrate dehydrogenase-1 (IDH1). For individuals with vulnerable IDH1 mutations, it has been demonstrated to be a very effective therapy for recurrent or refractory acute myeloid leukemia (AML). After a long review procedure, olutasidenib was finally given an approval by the FDA in December of 2022. To determine the concentration of olutasidenib in rat plasma, an LC-MS/MS approach was applied. The drug ibrutinib serves as a standard for comparison. Inertsil ODS, 150 mm × 4.6 mm, 3.5 μm, mobile phase was Acetonitrile (ACN), and Ammonium formate buffer (AmF), pH 3.0 (50 : 50 v/v) at 1.0 ml min⁻¹ was used for the separation process. Liquid–liquid extraction (LLE) was adopted for both olutasidenib and the Internal standard (IS). Proton adducts of olutasidenib and ibrutinib were observed at m/z 354.8589 and 239.8107 and m/z 441.573 and 372.1236 in MRM positive mode, correspondingly. The approach was shown accurate throughout a range of 3.0–60.0 ng ml⁻¹ and correlation values of (r²) ≥ 0.999.6 replicates including olutasidenib at 4 distinct QC levels were analyzed to determine intra-assay precision and accuracy; the Coefficient of variations (CV) were reported to be 3.41% to 0.58% to 0.31% to 0.36, and the accuracy ranged from 97.40, 99.69, 99.4, and 99.16%, respectively, for LOQQC, LQC, MQC, and HQC. In a pharmacokinetic investigation using rat plasma, this strategy has proven effective.