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

Journal of Pharmaceutical and Biomedical Analysis
Yinsong ZhuZiwei Huang

Abstract

DV1 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. ...Continue Reading

Citations

Feb 6, 2020·Experimental Biology and Medicine·Chaozai ZhangJing An
Jan 2, 2021·Forensic Science International : Synergy·Wing-Sum ChanBobbie Kwok-Keung Cheung

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