Cation-exchange high-performance liquid chromatography assay for the nigrostriatal toxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and its monoamine oxidase B generated metabolites in brain tissues

This paper describes a sensitive (1 pmol/mg tissue) and selective bioanalytical method for the quantitative estimation of the nigrostriatal toxicant 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and its monoamine oxidase B generated metabolites, the 1-methyl-4-phenyl-2,3-dihydropyridium species MPDP+and the 1-methyl-4-phenylpyridinium species MPP+. The method is based on initial separation of the analytes after treatment of brain tissue homogenates with 5% trichloroacetic acid. The soluble fraction is analyzed directly by cation-exchange high-performance liquid chromatography employing a diode array UV detector. Results obtained with this assay have provided the first evidence for the presence of MPDP+in the mouse brain following intravenous administration of MPTP.