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A sensitive, specific high-performance liquid chromatographic procedure was developed for the determination of plasma ethmozin levels. Basic plasma samples were partitioned with methylene chloride. The organic extract was washed with water and then evaporated to dryness under reduced pressure. The residue was redissolved in 0.2 ml of the mobile phase, consisting of hexane-tetrahydrofuran-methanol-water (66:27:6,30:0.7 v/v), and then chromatographed on a microporous silica column. With a variable-wavelength UV detector set at 268 nm, 10 ng of ethmozin/ml of plasma was measured. The utility of the method for human pharmacokinetic studies was demonstrated.

Morphine, codeine, normorphine, norcodeine, nalorphine, methadone, pentazocine, cyclazocine, meperidine and levallorphan were tested in vitro for activity as inhibitors of rat brain monoamine oxidase. Beta-phenylisopropylhydrazine and chlorpromazine were used, respectively, as strong and weak inhibitors to define the upper and lower limits of inhibitory activity. All test compounds, with the exception of methadone, were found to be weaker monoamine oxidase inhibitors than chlorpromazine. The log dose-response curve for methadone stretches across four orders of magnitude in concentration and, at low molar concentrations, the monoamine oxidase inhibitory activity of methadone is equivalent to the monoamine oxidase inhibitory activity of betaphenylisopropylhydrazine at equally low concentrations.

An electron-capture GLC method is described for oxycodone and its major metabolite, noroxycodone, in plasma and urine. The method involves extraction of the two substances into benzene-isopropranol at pH 10.4, followed by back-extraction into 0.1 N HCl. The acid phase is washed with hexane and made alkaline prior to reextraction into benzene-isopropanol. The solvent is removed by evaporation, and the heptafluorobutyryl derivatives of the test substances are formed. After removal of excess reagent, oxycodone and noroxycodone are quantitated by GLC. The characteristics of both substances, with respect to plasma levels in dogs and analgesic activity in mice, are reported. Isolation of noroxycodone from human urine and its identification by TLC, GLC, and mass spectrometry are described.