In vitro metabolism studies on oxamniquine and related compounds by chiral liquid chromatography.

Abstract A previously developed method based on α 1 -acid glycoprotein for the resolution of the enantiomers of the Pfizer antischistosomal drug oxamniquine was used to examine possible enantioselectivity in the in vitro microsomal hydroxylation of a metabolic precursor, UK-3883, but was found to be limited by the poor operational stability of the analytical column (“EnantioPac”) employed. As an alternative approach, a “Pirkle” covalently-bonded dinitrobenzoyl leucine column was used, with simple pre-column solute derivatization to the carbamate to improve chromatographic performance. The method allowed preliminary examination of the stereochemistry of the in vitro biotransformation, hydroxylation of UK-3883 to oxamniquine, which yielded evidence for substrate enantioselectivity in favour of the dextrorotatory enantiomer of UK-3883.