SPECIES VARIABILITY IN THE STEREOSELECTIVE N-OXIDATION OF PARGYLINE

The monoamine oxidase inhibitor pargyline (N-benzyl-N-methyl-2-propyny lamine) is known to undergo extensive in vitro microsomal N-oxidation, thought to be mediated predominantly by the flavin-containing monooxy genase (FMO) enzyme system. Formation of the pargyline N-oxide (PNO) m etabolite creates a chiral nitrogen centre and thus asymmetric oxidati on is possible. This study describes a reverse-phase high-performance liquid chromatographic (HPLC) method for the quantitation of PNO and a chiral-phase HPLC method for the determination of the enantiomeric ra tio of PNO. In vitro microsomal N-oxidation of pargyline was found to be highly steroselective in a number of species, with the (+)-enantiom er being formed preferentially. This metabolic transformation was ster eospecific when purified porcine hepatic FMO was used as the enzyme so urce. (C) 1994 Wiley-Liss, Inc.