IDENTIFICATION AND DETERMINATION OF PHASE-I METABOLITES OF PROPAFENONE IN RAT-LIVER PERFUSATE

Propafenone (PF) is a class IC antiarrhythmic agent. To study the mech anisms 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 d rug. 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 ionizatio ns. Three major metabolite peaks, whose protonated molecular ions were m/z 358, 358 and 300, were identified as a propafenone derivative hyd roxylated in the omega-phenyl ring (omega-OK-PF): 5-hydroxypropafenone (5-OH-PF), and N-despropylpropafenone (N-des-PF). The levels of omega -OH-PF, 5-OH-PF, N-des-PF and PF were determined simultaneously by HPL C with UV detection at 210 nm and a mobile phase of 0.03% triethylamin e 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 evapora tion of solvent under nitrogen. The results revealed that omega-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 pl asma. (C) 1998 Elsevier Science B.V. All rights reserved.