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Clinical Chemistry 21: 1658-1662, 1975;
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Clinical Chemistry, Vol 21, 1658-1662, Copyright © 1975 by the American Association for Clinical Chemistry

Therapeutic Monitoring of Anticonvulsant Drugs: Gas-Chromatographic Simultaneous Determination of Primidone, Phenylethylmalonamide, Carbamazepine, and Diphenylhydantoin

Charles J. Least Jr. 1, George F. Johnson 1, and Harvey M. Solomon 1

1 Therapeutic Drug Monitoring Laboratory, Department of Laboratory Medicine, The Johns Hopkins Hospital, Baltimore, Md. 21205

We describe a sensitive and precise gas-chromatographic method in which benzylmalonate methylester monoamide is used as the internal standard for the simultaneous determination of primidone, phenylethylmalonamide, carbamazepine, and diphenylhydantoin. The trimethylsilyl derivatives of the anticonvulsants are well separated from each other and from normal serum constituents. The lower limit of detection for each drug is 0.5 mg/liter when 1 ml of serum is analyzed. Withinrun precision (CV), established by analysis of 10 replicates, was as follows: primidone (5.4 mg/liter), 2.6%; phenylethylmalonamide (5.5 mg/liter), 1.6%; diphenylhydantoin (6.6 mg/liter), 3.8%; and carbamazepine (10.4 mg/liter), 3.2%. Fifty specimens were analyzed for primidone and 35 for diphenylhydantoin by a standard gas-chromatographic method involving on-column methylation and by the procedure we have developed. The mean value observed for primidone with the on-column alkylation procedure was 9.3 mg/liter and with our procedure was 9.6 mg/liter. When values for our assay were regressed against values for the standard method, the slope of the least-squares line was 0.936, the intercept was 1.00 mg/liter, and r was 0.939. The mean values observed for diphenylhydantoin by on-column methylation and with our procedure were both 12.6 mg/liter. When values for our assay were regressed against the standard method, the slope of the leastsquares line was 0.944, the intercept was 0.3 mg/liter, and r was 0.988


Key Words: toxicology • management of seizures • intermethod comparison

Submitted on June 26, 1975
Accepted on August 1, 1975






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Copyright © 1975 by the American Association for Clinical Chemistry.