[Detection of the preservative chlorphenesin in cosmetics by high-performance liquid chromatography].

A simple determination method for preservative chlorphenesin in cosmetics was developed. Cosmetic samples were dissolved in methanol. The sample solution was analyzed by high-performance liquid chromatography (HPLC) with ODS column, using water-methanol (55:45) or water-acetonitrile (3:1) adjusted to pH 2.5 with phosphoric acid as the mobile phase. Chlorphenesin was detected with ultraviolet light detection at 280 nm. A linear relation was obtained between the peak areas and the concentrations of chlorphenesin in the range of 1-500 microg/ml. The determination limit of chlorphenesin was 1-2 microg/ml. Recoveries of chlorphenesin spiked in lotion and milky lotion at the levels of 0.03% and 0.3% were 98.8-100.0%. This method was applied for cosmetics including 0.03% and 0.3% of chlorphenesin and their content corresponded with the determined values.

Syntheses of potential metabolites of a potent kappa-opioid receptor agonist, TRK-820.

Chemical syntheses of three kinds of potential metabolites of TRK-820, a potent kappa-opioid receptor agonist, were described. One of the potential metabolites 2, 17-N-dealkylated TRK-820, was synthesized starting from noroxycodone through 8 steps in 21% total yield. Glucuronidation of intermediate 10 and compound 1, the free base of TRK-820, was carried out stereoselectively to give 3-O-beta-D-glucuronides 15 and 16 in good yields, respectively. Syntheses of potential conjugated metabolites 3 and 4 were accomplished through 10 steps and 2 steps in 11% and 43% total yields, respectively. Among the potential metabolites of TRK-820, compounds 2 and 4 were identified as metabolites in human hepatocytes. The results of pharmacological studies of compounds 2, 3, and 4 are described.