Development of a UPLC-MS/MS method for determination of pimavanserin tartrate in rat plasma: Application to a pharmacokinetic study.

Journal: Journal of pharmaceutical analysis
Published Date: Jul 8, 2017

Abstract

A simple, rapid and sensitive method based on an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed and validated for the determination of pimavanserin in rat plasma. The analyte was extracted by protein precipitation with methanol and separated on an ACQUITY BEH C column (100 × 2.1 mm, 1.7 µm; Waters, USA), with an isocratic elution of acetonitrile-water containing 10 mM ammonium acetate (70:30, v/v), at a flow rate of 0.2 mL/min for 2.5 min. The analyte and clarithromycin (the internal standard) were detected and quantified in positive ion mode using multiple reaction monitoring transitions at / 428.2 → 223.0 for pimavanserin and / 748.5 → 589.5 for clarithromycin. Relative coefficient () for the calibration curve was more than 0.9980. The intra-day and inter-day precisions (relative standard deviation, RSD%) were less than 13.3% and 10.5%, respectively, and the accuracy (relative error, RE%) was within ± 11.5%. The analytical method was successfully applied to a routine pharmacokinetic study of pimavanserin in rats after oral administration at the dose of 10 mg/kg.

Authors

  • Shixiao Wang
    School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • Yang Wang
    Department of General Surgery The First People's Hospital of Yunnan Province, The Affiliated Hospital of Kunming University of Science and Technology Kunming China.
  • Shuang Gao
    School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • Yuanyuan Zhang
    National Clinical Research Center for Kidney Disease, State Key Laboratory for Organ Failure Research, Division of Nephrology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, Guangdong Province, China.
  • Hanpei Wang
    Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • Longshan Zhao
    School of Pharmacy, Shenyang Pharmaceutical University, No. 103, Wenhua Road, Shenyang 110016, PR China.
  • Kaishun Bi
    School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • Shaojie Wang
    Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • Xiaohui Chen
    School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.

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