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Pharmacokinetic and brain distribution study of an anti‐glioblastoma agent in mice by HPLC–MS/MS
Author(s) -
Li Yaxin,
Dano Raina,
Li Cathy,
Zhang Wenjing,
Lathia Justin D.,
Wang Bingcheng,
Su Bin
Publication year - 2022
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.5310
Subject(s) - pharmacokinetics , chemistry , protein precipitation , chromatography , formic acid , high performance liquid chromatography , selected reaction monitoring , tandem mass spectrometry , analyte , brain tissue , liquid chromatography–mass spectrometry , distribution (mathematics) , mass spectrometry , pharmacology , medicine , mathematical analysis , mathematics , anatomy
Previously compound I showed great anti‐glioblastoma activity without toxicity in a mouse xenograft study. In this study, a sensitive and rapid high‐performance liquid chromatography–tandem mass spectrometry (HPLC–MS/MS) method was developed and validated to investigate the pharmacokinetics and brain distribution of compound I in mice. The protein precipitation method was applied to extract the compound from mouse plasma and brain homogenates, and it was then separated using a Kinetex C 18 column with a mobile phase consisting of acetonitrile–0.1% formic acid water (50:50, v/v). The analytes were detected with multiple reaction monitoring for the quantitative response of the compounds. The inter‐ and intra‐day precisions were <8.29 and 3.85%, respectively, and the accuracy range was within ±7.33%. The method was successfully applied to evaluate the pharmacokinetics of compound I in mouse plasma and brain tissue. The peak concentration in plasma was achieved within 1 h. The apparent elimination half‐life was 4.06 h. The peak concentration of compound I in brain tissue was 0.88 μg/g. The results indicated that compound I was rapidly distributed and could cross the blood–brain barrier. The pharmacokinetic profile summarized provides valuable information for the further investigation of compound I as a potential anti‐glioblastoma agent.