Analysis of hydroxylated and demethylated metabolites of mephenytoin in man and laboratory animals using gas-liquid chromatography and high-performance liquid chromatography

J Chromatogr. 1982 Oct 8;232(1):93-100. doi: 10.1016/s0378-4347(00)86011-9.


Separation of urinary mephenytoin metabolites was evaluated under various gas-liquid chromatographic (GLC) and high-performance liquid chromatographic (HPLC) conditions. A simple and rapid alkylation procedure is described for GLC-using a nitrogen sensitive thermionic detector. The in situ formation of sodium methinylsulfinylmethide is used as base for the perpropylation of hydantoins and their metabolites. Normal-and reversed-phase HPLC of the underivatized compounds was performed using four different types of stationary phases. None of the GLC systems separated all the six hydantoin compounds tested, whereas, normal-and reversed-phase HPLC were able to obtain a complete separation of these compounds. The major metabolites of mephenytoin were 5-phenyl-5-ethylhydantoin, 3-methyl-5-(4-hydroxyphenyl)-5-ethylhydantoin and 5-(4-hydroxyphenyl)-5-ethylhydantoin in man, rat, mouse, rabbit, and guinea pig. 3-Methyl-5-phenyl-5-(2-hydroxyethyl)-hydantoin and 3-methyl-5-(3-hydroxyphenyl)-5-ethylhydantoin are major metabolites in the dog.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Chromatography, Gas
  • Chromatography, High Pressure Liquid
  • Dealkylation
  • Dogs
  • Guinea Pigs
  • Humans
  • Hydantoins / metabolism*
  • Hydroxylation
  • Mephenytoin / metabolism*
  • Mice
  • Rabbits
  • Rats


  • Hydantoins
  • Mephenytoin