Summary
A modified gas chromatographic procedure for the determination of unconjugated and conjugated 4-hydroxydiphenylhydantoin (4-OH-DPH) in urine has been developed.
Unconjugated 4-OH-DPH is determined after selective extraction with toluene — ether (1:1). For the assay of conjugated 4-OH-DPH, the urine is pre-extracted withisoamylalcohol before acid hydrolysis to avoid interference by the dihydrodiol metabolite of DPH. The sensitivity of the method is 0.1 µg per ml. The method has been used to determine the urinary metabolites in two adult volunteers, during steady state plasma concentrations of DPH and in the elimination phase.
Similar content being viewed by others
References
Atkinson, A.J., MacGee, J., Strong, J., Garteiz, D., Gaffney, T.E.: Identification of 5-meta-hydroxyphenyl-5-phenylhydantoin as a metabolite of diphenylhydantoin. Biochem. Pharmacol.19 2483–2491 (1970)
Berlin, A., Agurell, S., Borgå, O., Lund, L., Sjöqvist, F.: Micromethod for the determination of diphenylhydantoin in plasma and cerebrospinal fluid. A comparison between a gas chromatographic and a spectrophotometric method. Scand. J. clin. Lab. Invest.29 281–287 (1972)
Brochmann-Hanssen, E., Olawuy Oke, T.: Gas chromatography of barbiturates, phenolic alkaloids, and xanthine bases. Flash-heater methylation by means of trimethylanilinium hydroxide. J. pharm. Sci.58 370–371 (1969)
Butler, T.C.: The metabolic conversion of 5,5-diphenyl-hydantoin to 5-(p-hydroxyphenyl)-5-phenylhydantoin. J. Pharmacol. exp. Ther.119 1–11 (1957)
Chang, T., Okerholm, R.A., Glazko, A.J.: A 3-0-methylated catechol metabolite of diphenylhydantoin (Dilantin) in rat urine. Res. Commun. chem. Pathol. Pharmacol.4 13–23 (1972)
Chang, T., Savory, A., Glazko, A.J.: A new metabolite of 5,5-diphenylhydantoin (Dilantin). Biochem. biophys. Res. Commun.38 444–449 (1970)
Dill, W.A., Kazenko, A., Wolf, L., Glazko, A.J.: Studies on 5,5-diphenylhydantoin (Dilantin) in animals and man. J. Pharmacol. exp. Ther.118 270–279 (1956)
Estas, A., Dumont, P.A.: Simultaneous determination of 5,5-diphenylhydantoin and 5-(p-hydroxyphenyl)-5-phenylhydantoin in serum, urine and tissues by gas-liquid chromatography after flash-heater methylation. J. Chromat.82 307–314 (1973)
Gabler, W.L., Hubbard, G.L.: The metabolism of 5,5-diphenyl-hydantoin (DPH) in nonpregnant and pregnant rhesus monkeys. Arch. int. Pharmacodyn.203 72–91 (1973)
Glazko, A.J., Chang, T., Baukema, J., Dill, W.A., Goulet, J.R., Buchanan, R.A.: Metabolic dispositon of diphenylhydantoin in normal human subjects following intravenous administration. Clin. Pharmacol. Ther.10 498–504 (1969)
Henze, H.R., Isbell, A.F.: Researches on substituted 5-phenyl-hydantoins. J. Amer. chem. Soc.76 4152–4156 (1954)
Lund, L., Alván, G., Berlin, A., Alexanderson, B.: Pharmacokinetics of single and multiple doses of phenytoin in man. Europ. J. clin. Pharmacol.7 81–86 (1974)
MacGee, J.: Rapid determination of diphenylhydantoin blood plasma by gas-liquid chromatography. Analyt. Chem.42 421–422 (1970)
Maynert, E.W.: The metabolic fate of diphenylhydantoin in the dog, rat and man. J. Pharmacol. exp. Ther.130 275–284 (1970)
Rane, A., Garle, M., Borgå, O., Sjöqvist, F.: Plasma disappearance of transplacentally transferred phenytoin (diphenylhydantoin) in the newborn studied with mass fragmentography. Clin. Pharmacol. Ther.15 39–45 (1974)
Rane, A.: Urinary excretion of diphenylhydantoin metabolites in newborns. J. Pediat.85 543–545 (1974)
Author information
Authors and Affiliations
Additional information
To the memory of Balzar Alexanderson
Rights and permissions
About this article
Cite this article
Karlén, B., Garle, M., Rane, A. et al. Assay of the major (4-hydroxylated) metabolites of diphenylhydantoin in human urine. Eur J Clin Pharmacol 8, 359–363 (1975). https://doi.org/10.1007/BF00562663
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00562663