Determination and metabolism of brexpiprazole following baicalin to rats by a novel developed UPLC-MS/MS

The prime purpose of this research currently being done was to set up an acceptable and high-operational ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method, which could simultaneously analyze the concentration levels of brexpiprazole, assisted medication for treating depression, and DM-3411, the principal metabolite of brexpiprazole in rats, and to examine the impact of baicalin on the metabolism of brexpiprazole in rats. After quick sample preparation using acetonitrile as a protein precipitating agent, the chromatograms of brexpiprazole, DM-3411 and aripiprazole (internal standard, IS) were successfully separated by Acquity BEH C18 (2.1 mm × 50 mm, 1.7 μm) column. The concentrations of the analytes were detected through a Xevo TQ-S triple quadrupole tandem by the positive ion scanning. The ranges of calibration curves for both brexpiprazole and DM-3411 were 0.5–100 ng/mL, and the approach represented fine linearity in the ranges. The lower limit of quantification (LLOQ) of brexpiprazole and DM-3411 could reach 0.5 ng/mL in the study. The range of intra-day and inter-day accuracy of the two analytes was between −10.6% and 12.3%, while the precision was ≤ 11.5%. The recovery rate of each compound was greater than 81.0%, and no obvious matrix effects were observable. In addition, the plasma sample quantitative detection of the compounds in the study remained stable under all conditions. Then, we used this assay to detect the plasma levels of brexpiprazole and DM-3411 from a herb-drug interaction investigation, in which 200 mg/kg baicalin remarkably increased the plasma concentration of brexpiprazole and changed brexpiprazole pharmacokinetics. This study will contribute to a better understanding of the pharmacokinetic properties of brexpiprazole when concurrent use with baicalin, and to an understanding of the unanticipated clinical risks.