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A simple, rapid, and accurate method is described for determining diphenylhydantoin concentrations in plasma. An internal standard, primidone (primaclone), is added to 2 ml of acidified plasma, and primidone and diphenylhydantoin are extracted into chloroform. The extract, washed with hexane and concentrated, is injected into a gas chromatograph. Extraction and measurement of a single sample requires about 30 min, and as many as 40 samples can be assayed in a working day. Both therapeutic and overdose concentrations of diphenylhydantoin in plasma can be detected and measured. Nine other acidic drugs, added to plasma samples, did not interfere with the analysis.
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Sampson et al. (1971) studied this question.
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