Development of a liquid chromatography assay for the determination of opicapone and BIA 9–1079 in rat matrices. (17th August 2015)

• Record Type: Journal Article
• Authors: Gonçalves, Daniela; Alves, Gilberto; Fortuna, Ana; Soares‐da‐Silva, Patrício; Falcão, Amílcar
• Is Part Of: Biomedical chromatography. Volume 30:Number 3(2016:Mar.)
• Page Start: 312
• Page End: 322
• Publication Date: 2015-08-17
• Subjects: opicapone -- catechol‐O‐methyltransferase inhibitor -- rat -- method validation -- HPLC‐DAD; Chromatographic analysis -- Periodicals; Biology -- Periodicals; Medicine -- Periodicals; Biology -- Periodicals; Chromatography -- methods -- Periodicals; Medicine -- Periodicals; 543.089
• DOI: 10.1002/bmc.3550
• Languages: English
• ISSNs: 0269-3879

Abstract

Abstract: Opicapone is a novel potent, reversible and purely peripheral third generation catechol‐ O ‐methyltransferase inhibitor, currently under clinical trials as an adjunct to levodopa therapy for Parkinson's disease. To support additional nonclinical pharmacokinetic studies, a novel high‐performance liquid chromatographic method coupled to a diode array detector (HPLC‐DAD) to quantify opicapone and its active metabolite (BIA 9–1079) in rat plasma and tissues (liver and kidney) is herein reported. The analytes were extracted from rat samples through a deproteinization followed by liquid‐liquid extraction. Chromatographic separation was achieved in less than 10 min on a reversed‐phase C18 column, applying a gradient elution program with 0.05 M monosodium phosphate solution (pH 2.45 ± 0.05) and acetonitrile. Calibration curves were linear ( r 2 ≥ 0.994) within the ranges of 0.04‐6.0 µg/mL for both analytes in plasma, 0.04‐4.0 µg/mL for opicapone in liver and kidney homogenates, and 0.07‐4.0 µg/mL and 0.06‐4.0 µg/mL for BIA 9–1079 in liver and kidney homogenates, respectively. The overall intra‐ and inter‐day accuracy ranged from −12.68% to 7.70% and the imprecision values did not exceed 11.95%. This new HPLC‐DAD assay was also successfully applied to quantify opicapone and BIA 9–1079 in a preliminary pharmacokinetic study. Copyright © 2015 John Wiley & Sons, Ltd.