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  • Title: Sensitive GLC procedure simultaneous determination of phenytoin and its major metabolite from plasma following single doses of phenytoin.
    Author: Midha KK, McGilveray IJ, Wilson DL.
    Journal: J Pharm Sci; 1976 Aug; 65(8):1240-3. PubMed ID: 978445.
    Abstract:
    An improved GLC procedure was developed for the simultaneous determination of phenytoin and its metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin, in plasma and urine following enzyme hydrolysis. After extraction, the drug, the metabolite, and the internal standard, 5-(p-methylphenyl)-5-phenylhydantoin, are measured by GLC with flame-ionization detection as their respective methyl derivatives following flash-heater methylation with trimethylanilinium hydroxide. The drug and metabolite give well-resolved symmetrical peaks on a phenyl methyl silicone column, and the method has a sensitivity of 150 ng/ml of phenytoin and 125 ng/ml of the metabolite. GLC-mass spectral evidence is presented for the formation and intact determination of methyl derivatives of the drug, its metabolite, and the internal standard.
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