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High‐Performance liquid chromatographic resolution of oxamniquine enantiomers: Application to in vitro metabolism studies
Author(s) -
Noctor Terence A. G.,
Fell Anthony F.,
Kaye Barry
Publication year - 1990
Publication title -
chirality
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.43
H-Index - 77
eISSN - 1520-636X
pISSN - 0899-0042
DOI - 10.1002/chir.530020413
Subject(s) - chemistry , chromatography , oxamniquine , enantiomer , biotransformation , high performance liquid chromatography , residue (chemistry) , ether , column chromatography , detection limit , extraction (chemistry) , enzyme , stereochemistry , biochemistry , organic chemistry , zoology , praziquantel , biology , helminths , schistosomiasis
A method is described for the HPLC analysis of oxamniquine enantiomers in liver fraction incubates, using a second‐generation α 1 ‐acid glycoprotein‐based column (Chiral‐AGP). Oxamniquine is extracted from the incubation media by liquid–liquid extraction, using diethyl ether. The dried residue is redissolved in eluent, filtered, then injected directly onto the analytical column. The extraction method affords recoveries of oxamniquine of approximately 93%, at concentrations up to 525 μg/ml, with an average relative standard deviation of 5.9%. The limit of detection of the method (to give an SNR = 2 at 246 nm) is 0.3 ng on‐column for the first eluting, laevorotatory enantiomer and 2.3 ng for the dextrorotatory isomer. The method allowed study of the depletion of oxamniquine enantiomers in liver postimicrosomal incubates. In the rat, a turnover of 21.9% was observed, with no apparent enantioselectivity. Similar observations were made for a mouse liver subcellular fraction incubation. The absence of enantioselectivity in this biotransformation may be attributable to the low substrate specificity of the oxidase or dehydrogenase enzymes involved.