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Pharmacokinetics and metabolism of LNP023 in rats by liquid chromatography combined with electrospray ionization–tandem mass spectrometry
Author(s) -
Jiang Xianglan,
Pan Rongrong
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.5006
Subject(s) - chemistry , chromatography , formic acid , electrospray ionization , selected reaction monitoring , pharmacokinetics , glucuronidation , mass spectrometry , liquid chromatography–mass spectrometry , acetonitrile , tandem mass spectrometry , high performance liquid chromatography , organic chemistry , medicine , enzyme , microsome
Abstract In this study, a simple and sensitive LC–tandem mass spectrometric method was developed and validated for the determination of LNP023 in rat plasma. The plasma sample was precipitated with acetonitrile and then separated on an ACQUITY HSS T 3 column (50 mm × 2.1 mm, 1.8 μm) using 0.1% formic acid in water and acetonitrile as the mobile phase. The MS detection was performed in positive multiple‐reaction monitoring mode with precursor‐to‐product ion transitions of m/z 423.3 → 174.1 and m/z 435.3 → 367.1 for LNP023 and olaparib (internal standard), respectively. The developed assay was validated in the linear range of 0.1–1000 ng/mL with correlation coefficient ( r ) greater than 0.9992. The validation parameters were all within the acceptable limits. The validated method has been successfully used to investigate the pharmacokinetics of LNP023 in rat plasma, and our results indicated that LNP023 showed low clearance and high bioavailability (62.2%). Furthermore, four minor metabolites from rat plasma were detected and identified by LC combined with high‐resolution mass spectrometry. The metabolic pathways were O ‐deethylation (M1), hydroxylation (M4), oxidation (M3), and acyl‐glucuronidation (M2).