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NIH Research Festival

September 12 – 14, 2018

Development of a quantitative bioanalytical method for the assessment of benserazide pharmacokinetics in pre-clinical studies

Thursday, September 13, 2018 – Poster Session IV
3:30 – 5:00 p.m.

FAES Terrace

NCATS

PHARM-6

Authors

  • Amy Wang
  • K Konrath
  • G Dunn
  • E Hughes
  • M Singleton
  • S Haugabook
  • S Perrine-Faller
  • Xin Xu

Abstract

Benserazide is a peripherally-acting DOPA decarboxylase inhibitor. It has been used to inhibit amino acid decarboxylase to enhance plasma and brain levels of levodopa for the treatment of Parkinson's disease and restless legs syndrome in European Union and other countries; but has not been approved in the United States. Recently, the compound has been identified as a potent inducer of fetal globin expression and is considered as a drug candidate for the treatment of -hemoglobinopathies. The objective of this study is to develop an accurate, sensitive and selective UPLC–MS/MS method, evaluate the benserazide stability in blood and plasma, establish the PK sample collection procedures to maintain compound ex vivo stability, and assess pharmacokinetics of the compound in lab animals. The quantitative bioanalysis of benserazide in biological matrices faces a number of challenges, including instability at pH 7.4, hydrophilicity, low molecular weight, and endogenous interference. With these challenges in mind, a novel method for the quantification of benserazide in plasma samples has been developed using HILIC UPLC-MS/MS. The developed method has a linear calibration range of 1.0 ng/mL to 1000 ng/mL using 30 µL plasma and protein precipitation sample preparation. The optimized HILIC-UPLC-MS/MS method provided good chromatographic retention for benserazide, separated analyte from the endogenous interference, and reduced the sample preparation and analysis time. The developed HILIC-UPLC-MS/MS method was utilized in preclinical PK studies.

Scientific Focus Area: Molecular Pharmacology

This page was last updated on Friday, March 26, 2021

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2018 program

Download the 2018 Research Festival Schedule Overview (6 pages)

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