Rapid quantitative determination of underivatized carbamazepine, phenytoin, phenobarbital and p-hydroxyphenobarbital in biological fluids by packed column gas chromatography.

A method is described for measuring, without derivatization, the concentrations of phenobarbital, p-hydroxyphenobarbital, carbamazepine and phenytoin in biological fluids of epileptic patients undergoing long-term therapy. This method uses, at an isothermal temperature, a special column packing (GP-2% SP-2510-DA on 100-120 mesh Supelcoport). The lower limit of detection for all substances analyzed is 1 microgram/ml of biological material. The recovery of the compounds is about 95%, the reproducibility of the method is good (coefficient of variation, 4.3%). The mass spectra confirm the identity of substances eluting from the column. There is no interference from other commonly used antiepileptic drugs or endogenous substances. The method has the advantages of high specificity, sensitivity and rapidity and it appears to be suitable for the routine monitoring of blood and urine concentrations in patients receiving multi-drug therapy.