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Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions
Published on: December 1, 2020
Bioanalytical method development and validation for determination of olutasidenib and its application to
Madhusudhana Reddy Nimmakayala1, Kuruva Rangamuni1, Jasti Surendra2
1Department of Chemistry, Koneru Lakshmaiah Education Foundation Green Fields, Vaddeswaram Guntur Andhra Pradesh 522302 India atluri.deepti1984@gmail.com +91 9490494699.
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 (r 2) ≥ 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.
Insights
A new LC-MS/MS method accurately measures olutasidenib in rat plasma for pharmacokinetic studies. This validated approach supports the use of olutasidenib (IDH1 inhibitor) for acute myeloid leukemia (AML) treatment.
Area of Science:
- Pharmacology and Toxicology
- Analytical Chemistry
- Oncology
Background:
- Olutasidenib is an FDA-approved inhibitor targeting isocitrate dehydrogenase-1 (IDH1) mutations.
- It is an effective therapy for relapsed or refractory acute myeloid leukemia (AML) with susceptible IDH1 mutations.
- FDA approval was granted in December 2022 following an extensive review process.
Purpose of the Study:
- To develop and validate a sensitive and accurate liquid chromatography-tandem mass spectrometry (LC-MS/MS) method.
- To determine the concentration of olutasidenib in rat plasma.
- To support pharmacokinetic investigations of olutasidenib.
Main Methods:
- Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was employed for analysis.
- Ibrutinib was used as an internal standard for comparison.
- Liquid-liquid extraction (LLE) was utilized for sample preparation.
- A specific Inertsil ODS column and a mobile phase of Acetonitrile (ACN) and Ammonium formate buffer (AmF) were used for separation.
Main Results:
- The LC-MS/MS method demonstrated high accuracy within a concentration range of 3.0-60.0 ng/mL, with correlation coefficients (r²) ≥ 0.999.
- Intra-assay precision showed coefficients of variation (CV) ranging from 0.31% to 3.41%.
- Accuracy ranged from 97.40% to 99.69% across different quality control levels.
Conclusions:
- The developed LC-MS/MS method is accurate, precise, and effective for quantifying olutasidenib in rat plasma.
- This validated method is suitable for pharmacokinetic studies of olutasidenib.
- The findings contribute to the understanding of olutasidenib's behavior in vivo, aiding its therapeutic application in AML.
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