Improved determination of phenobarbital, primidone, and phenytoin by use of a preparative instrument for extraction, followed by gas chromatography.

A microprocessor-controlled automatic extractor, (PREMTM I) is described with which lipophilic components may be extracted from physiological fluids by means of a selective, solid-phase extraction cartridge, and the extracts presented in dry form for subsequent analysis. This instrument has been successfully evaluated for the extraction of phenobarbital, primidone, and phenytoin from human serum before chromatographic analysis. We describe a specific method for determination of these anticonvulsants, involving the PREP I and analysis, after flash-heater methylation, in a gas chromatograph equipped with a nitrogen-sensitive detector. Absolute recoveries ranged from 90 to 102%. Within-day and day-to-day precision (CV) ranged from 4 to 7% for all three drugs in therapeutic concentrations. Comparison of this method with results obtained with a liquid--liquid micro-scale extraction and a similar gas-chromatographic method resulted in correlation coefficients of 0.988 (phenobarbital), 0.978 (primidone), and 0.982 (phenytoin). These drugs in therapeutic concentrations can be simultaneously extracted and measured with confidence.