Identification of p-hydroxyprimidone as a minor metabolite of primidone in rat and man

Urine specimens from rats and humans who received single doses of primidone (PRM) have been investigated by GC/MS procedures. In addition to the previously documented metabolites of PRM, a small chromatographic peak was encountered which had a mass spectrum suggesting a hydroxy-PRM derivative. Synthesis of p-hydroxy-PRM from PRM was effected; the para isomer was separated from unwanted isomers by preparative HPLC. The PMR spectrum of the synthetic compound proved the position of the hydroxy substituent to be para. This compound had identical GC retention time and an almost identical mass spectrum with that obtained in the urinary extracts. Para-hydroxy-PRM was therefore confirmed as a new, minor metabolite of PRM in rat and man.