Analysis of Narcotics. IV

Studies on Non-aqueous Titration

Abstract

Titration curves of codeine and thebaine were compared on titration with p-toluenesulfonic acid in chloroform, acetic acid, dioxane, or 1:1-volume mixture of ethylene glycol and isopropanol and it was found that the curve became gradual in the order of chloroform, dioxane, ethylene glycol-isopropanol, and acetic acid. The coefficient of cubical expansion of solvents often used for non-aqueous titration was measured and it was found that the coefficient of the 1:1 mixture of ethylene glycol-isopropanol is 2.5 times and those of the other solvents 3-4 times that of water. It also showed that acetic acid, which had often been used to date, is not very satisfactory. The coefficient decreases in the order of benzene, chloroform, methanol, isopropanol, acetic acid, dioxane, ethylene glycol-isopropanol, and ethylene glycol. Good results were obtained by the non-aqueous titration of morphine, codeine, thebaine, dihydrocodeine, papaverine, hydroxydihy drocodeinone, and hydrocotarnine by dissolving about 20mg. of each in a chloroform-phenol mixture and titratiog with 0.005N p-toluenesulfonic acid in 1:1 volume mixture of ethylene glycol and isopropanol, using methyl orange as the indicator. A minute amount of the narcotics was determined in a 100-times diluted powder of codeine and dihydrocodeine phosphate, and a cherry bark extract containing 2mg. of dihydrocodeine phosphate in each tablet. The error was within 0.6% in the former two and about 1% in the latter.