Ww. Tan et al., IDENTIFICATION AND DETERMINATION OF PHASE-I METABOLITES OF PROPAFENONE IN RAT-LIVER PERFUSATE, Journal of pharmaceutical and biomedical analysis, 16(6), 1998, pp. 991-1003
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.