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Quantification and pharmacokinetic property of verubecestat an BACE1 inhibitor in rat plasma
Author(s) -
Wang Qiong,
Wang Haiyun,
Zhong Youyan,
Mei Yibin
Publication year - 2020
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.4715
Subject(s) - chemistry , chromatography , protein precipitation , analyte , formic acid , bioanalysis , electrospray ionization , selected reaction monitoring , acetonitrile , sample preparation , pharmacokinetics , elution , extraction (chemistry) , mass spectrometry , tandem mass spectrometry , analytical chemistry (journal) , medicine
In the present study, an ultra‐performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) approach was designed to measure the rat plasma levels of verubecestat with diazepam as the internal standard. Acetonitrile‐based protein precipitation was applied for sample preparation, then the analyte verubecestat was subjected to gradient elution chromatography with a mobile phase composed of acetonitrile (A) and 0.1% formic acid in water (B). Verubecestat was monitored by m/z 410.1 → 124.0 transition for quantification by multiple reaction monitoring (MRM) in positive ion electrospray ionization (ESI) source. When the concentration of verubecestat ranged from 1 to 2500 ng/mL, the method exhibited good linearity. For verubecestat, the intra‐ and inter‐day precision were determined with the values of 2.9–9.0% and 0.4–6.5%, respectively; and the accuracy ranged from −2.2% to 10.4%. Matrix effect, extraction recovery, and stability data were in line with the standard FDA guidelines for validating a bioanalytical method. The validity of the developed method was confirmed through the pharmacokinetic study.