LC–MS/MS assay for the determination of a novel D-peptide antagonist of CXCR4 in rat plasma and its application to a preclinical pharmacokinetic study

Publication date: Available online 17 August 2018Source: Journal of Pharmaceutical and Biomedical AnalysisAuthor(s): Yinsong Zhu, Shu Yang, Juan Wang, Yujia Mao, Yan Xu, Jing An, Ziwei HuangAbstractDV1 is a potent and selective D-peptide antagonist of CXCR4 and being developed as a novel drug candidate molecule. For preclinical pharmacokinetic study of DV1, we established an efficient and reliable liquid chromatography coupled to tandem mass spectrometric (LC–MS/MS) method for the assay of DV1 in rat plasma. Plasma samples were acidified by formic acid and then their protein content precipitated by acetonitrile. Sample separation was processed with a C18 column (4.6 mm × 100 mm, 5 μm) and washed by a water-acetonitrile gradient mobile phase containing 0.1% (v/v) formic acid at a flow rate of 0.4 mL/min. The mass spectrometer was operated in the multiple reaction monitoring mode and positive electrospray ionization. The assay had a good linearity over the range of 10-10000 ng/mL (r>0.998) for DV1. The adsorption of the peptide was diminished by organic additives during the quantitative procedure. The intra- and inter-day precision was 1.9–9.8 % and the accuracy was 91.2–110.0%. No significant variation was observed under the optimized conditions. The recovery was above 52 % with low matrix effects. The method was successfully applied to a pharmacokinetic study of DV1 after subcutaneous injection at dose of 10 mg/kg in rats. The half-life and AUCinf of D...
Source: Journal of Pharmaceutical and Biomedical Analysis - Category: Drugs & Pharmacology Source Type: research