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An enantioselective gas chromatographic assay utilising electron-capture detection has been developed for the simultaneous quantitation of enantiomers of fenfluramine and norfenfluramine in plasma. The assay involves the conversion of the enantiomers of both fenfluramine and norfenfluramine into their corresponding diastereomeric amide derivatives by an acylation reaction with n-heptafluorobutyryl-S-prolyl chloride under Schotten—Baumann conditions prior to gas chromatographic separation on an achiral polar OV-225 capillary column. Linear and reproducible standard curves were obtained over the concentration ranges 4.30–86.3 ng/ml per enantiomer and 1.25–42.25 ng/ml per enantiomer for the enantiomers of fenfluramine and norfenfluramine, respectively. The method was applied to a single-dose pharmacokinetic study in a healthy adult subject. Stereoselective differences were observed in the plasma concentration versus time profiles of the enantiomers of both fenfluramine and norfenfluramine. The area under the plasma concentration versus time curve values obtained for the l-isomers of fenfluramine or norfenfluramine were higher than the values of their corresponding d-antipodes.

A new sensitive high-performance liquid chromatographic method for indomethacin from plasma on a reversed-phase column (C18) has been developed. The method involves precipitation of plasma with perchloric acid followed by diethyl ether extraction. The assay is quantitative down to 0.25 microgram ml-1 from a 200-microliters aliquot of plasma with a detection limit of 0.1 microgram ml-1 and a recovery of approximately 90%. The method was applied to single-dose studies with volunteers under various dietary restrictions. The results of these studies indicated that intrasubject variability within these regimens may be as important a factor as the intersubject variability already documented for this drug. These results have important implications in the determination of bioavailability and pharmacokinetic parameters of this drug.

A procedure is described for the quantitative determination of metronidazole (1-β-hydroxyethyl-2-methyl-5-nitroimidazole) in human plasma. After extraction from plasma, metronidazole and the internal standard, 1-β-hydroxyethyl-2-methoxy-5-nitroimidazole, are converted to trimethylsilyl derivatives for injection into a gas chromatograph. Detection by means of a flame ionization detector allowed concentrations of 0.25 μg of metronidazole per ml plasma to be determined with a precision of 6%. Application of the assay to obtain profiles of metronidazole in plasma of dog and man after single doses of 12 mg/kg and 250 mg, respectively, are reported.