Title:Determination of Mefuparib in Rat Plasma and its Application to Pharmacokinetics by a Simple and Rapid UPLC-MS/MS
Volume: 20
Issue: 5
Author(s): Lianguo Chen, Longquan Lin, Rongbin Jiang, Jialei Wu, Congcong Wen and Xianqin Wang*
Affiliation:
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
Keywords:
UPLC-MS/MS, rat, bioavailability, pharmacokinetics, CVL218, poly-ADP-ribose.
Abstract:
Objectives: Mefuparib (CVL218) is one of the second-generation poly-ADP-ribose polymerase
(PARP) inhibitors and is used for the treatment of cancer. In this work, the levels of
CVL218 in the plasma samples of rats were measured using a newly developed UPLC-MS/MS
method.
Methods: Six rats were given CVL218 (3 mg/kg) orally (po), and another six rats received
CVL218 (1 mg/kg) intravenously (iv). Rat plasma samples were treated with acetonitrile-
methanol (1:1, v/v) for protein precipitation. Cilostazol was used as the internal standard.
Over the range of 0.9–450 ng/mL, a standard curve representing known concentrations of
CVL218 in blank rat plasma was produced by UPLC-MS/MS. The US Food and Drug Administration
(FDA) guidelines were followed in the development of the validation method.
Results: In rat plasma, the accuracy ranged from 90% to 112%, and the intra-day precision and inter-
day precision were both less than 15%. The recovery was higher than 87% and the matrix effect
varied from 102% to 113%. In the intravenous and oral administration groups, the values of
AUC(0-t) were 227.5 ±21.6 and 217.0 ±15.5 ng/mL·h, respectively, and the bioavailability was
31.8%. Furthermore, the half-life (T1/2) for oral and intravenous administration was found to be 1.6
±0.7 h and 1.7 ±0.3 h, respectively.
Conclusion: The developed UPLC-MS/MS method was successfully applied to the determination
of CVL218 in rat plasma following oral and intravenous administration.
