Identification and determination of phase I metabolites of propafenone in rat liver perfusate |
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| Institution: | 1. Applied Physics, Faculty of Science and Technology, Suan Sunandha Rajabhat University, Bangkok 10300, Thailand;2. Optical Thin-Film Laboratory, National Electronics and Computer Technology Center, Pathumthani 12120, Thailand;3. Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, 40132, Indonesia;1. Glass and Materials Technology (GMAT) Group, Department of Physics, Faculty of Science and Technology, Muban Chombueng, Rajabhat University, Ratchaburi 70150, Thailand;2. Department of Tool and Materials Engineering, Faculty of Engineering, King Mongkut’s University of Technology Thonburi (KMUTT), Bangkok 10140, Thailand;1. Center of Excellence in Glass Technology and Materials Science (CEGM), Nakhon Pathom Rajabhat University, Nakhon Pathom 73000, Thailand;2. Physics Program, Faculty of Science and Technology, Nakhon Pathom Rajabhat University, Nakhon Pathom 73000, Thailand;3. Department of Physics, Faculty of Mathematics and Natural Sciences, Institut Teknologi Bandung, 40132, Indonesia;4. Informatics Mathematics, Faculty of Science and Technology, Suan Sunandha Rajabhat University, Bangkok 10300, Thailand;5. Applied Physics, Faculty of Science and Technology, Suan Sunandha Rajabhat University, Bangkok 10300, Thailand;1. Energy Engineering Technology Program, College of Industrial Technology, King Mongkut’s University of Technology North Bangkok, Bangkok 10800, Thailand;2. Building Energy Expert, 12 Place du soleil, 38920 Crolles, France;1. Physics Program, Nakhon Pathom Rajabhat University, Nakhon Pathom 73000, Thailand;2. Center of Excellence in Glass Technology and Materials Science (CEGM), Nakhon Pathom Rajabhat University, Nakhon Pathom 73000, Thailand;3. Department of Physics, Faculty of Mathematics and Natural Sciences, Universitas Negeri Medan, 20221, Indonesia |
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| Abstract: | Propafenone (PF) is a class 1C antiarrhythmic agent. To study the mechanisms of PF interactions with dietary nutrients in isolated, perfused rat livers, metabolites of PF in liver perfusate were identified and an analytical method was developed for these metabolites plus parent drug. Identification of phase I metabolites was performed using HPLC/MS equipped with a Lichrospher RP-18 column and tandem mass spectrometry (MS/MS) with electrospray and atmospheric pressure chemical ionizations. Three major metabolite peaks, whose protonated molecular ions were m/z 358, 358 and 300, were identified as a propafenone derivative hydroxylated in the ω-phenyl ring (ω-OH-PF), 5-hydroxypropafenone (5-OH-PF), and N-despropylpropafenone (N-des-PF). The levels of ω-OH-PF, 5-OH-PF, N-des-PF and PF were determined simultaneously by HPLC with UV detection at 210 nm and a mobile phase of 0.03% triethylamine and 0.05% phosphoric acid in water-acetonitrile-methanol (45:20:35, v/v/v) after extraction with 5 ml diethyl ether at pH 10.0 and evaporation of solvent under nitrogen. The results revealed that ω-OH-PF, which was not found in humans, was the major metabolite of PF in rat liver perfusate, not 5-OH-PF which is the major metabolite in human plasma. |
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