Ultramicro gas-chromatographic analysis for anticonvulsants, with use of a nitrogen-selective detector.

Abstract

We describe a procedure for determining phenobarbital, primidone, and diphenylhydantoin simultaneously in 50-mul volumes of serum by use of gas chromatography and a detector with heightened sensitivity and selectivity for nitrogenous compounds. The drugs, together with an internal standard, 5-allyl-5-phenyl barbituric acid, are extracted from serum by the procedure of MacGee [Anal. Chem. 42, 421 (1970)]. The drugs are converted to their methyl derivatives by a modification of the procedure of Greeley [Clin. Chem. 20, 192 (1974)] and then analyzed on a column containing 3% OV-1, with a temperature program, and detected by a nitrogen-selective detector. The method is reproducible to about 7%. Sensitivities of 0.5 mg/liter for 50-mul serum samples are attained routinely. Mephobarbital interferes with the analysis because methylation yields the same product as methylated phenobarbital. Total analysis time for a single sample is 15 min.