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Validated HPLC‐UV method for simultaneous quantification of phosphatidylinositol 3‐kinase inhibitors, copanlisib, duvelisib and idelalisib, in rat plasma: Application to a pharmacokinetic study in rats
Author(s) -
Siddesh Anup,
Sriram Dhurvu,
Zakkula Ashok,
Kumar Rajnish,
Dittakavi Sreekanth,
Zainuddin Mohd,
Trivedi Ravi Kumar,
Mullangi Ramesh
Publication year - 2021
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.5015
Subject(s) - chromatography , chemistry , analyte , idelalisib , pharmacokinetics , extraction (chemistry) , high performance liquid chromatography , elution , calibration curve , detection limit , pharmacology , leukemia , chronic lymphocytic leukemia , medicine , ibrutinib
Phosphatidylinositol 3‐kinase (PI3K) inhibitors are a novel class of anticancer drugs that are approved to treat various malignancies. We report the development and validation of a HPLC method for the simultaneous quantitation of three PI3K inhibitors, namely copanlisib, duvelisib and idelalisib, in rat plasma as per the regulatory guidelines of the United States Food and Drug Administration. The method involves extraction of copanlisib, duvelisib and idelalisib along with an internal standard (IS; filgotinib) from rat plasma (100 μL) using a liquid–liquid extraction process. The chromatographic separation of the analytes was achieved using step‐wise gradient elution on a Hypersil Gold C 18 column. The UV detection wavelength was set at λ max = 280 nm. Copanlisib, duvelisib, idelalisib and the IS eluted at 7.16, 12.6, 11.9 and 9.86 min, respectively, with a total run time of 15 min. The calibration curve ranged from 50 to 5000 ng/mL for all the analytes. Inter‐ and intra‐day precision and accuracy, stability studies, dilution integrity and incurred sample reanalysis were investigated for all three analytes, and the results met the acceptance criteria. The validated HPLC method was successfully applied to a pharmacokinetic study in rats.