Quantification and pharmacokinetic property of verubecestat an BACE1 inhibitor in rat plasma.

Quantification and pharmacokinetic property of verubecestat an BACE1 inhibitor in rat plasma. Biomed Chromatogr. 2019 Oct 21;:e4715 Authors: Wang Q, Wang H, Zhong Y, Mei Y Abstract 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. PMID: 31633829 [PubMed - as supplied by publisher]
Source: Biomedical Chromatography : BMC - Category: Biomedical Science Authors: Tags: Biomed Chromatogr Source Type: research