No abstract

NON-AQUEOUS titrimetry has been applied to the assay of barbiturates by several groups of workers. Autian and Allen' developed a potentiometric method using a solvent system of chloroform and polyethylene glycol 400. Their studies were modified and extended by Swartz and Foss2, but these workers also failed to find a suitable indicator for this solvent system. They expressed a desire to employ chloroform alone, which is an excellent solvent for most barbituric acids, but found that such a titration was not suitable as precipitation of the barbiturate salts obscured the indicator end-point. Because of its low dielectric constant, chloroform was also a poor solvent for potentiometric titrations. They circumvented this difficulty by adding 10 per cent. polyethylene glycol 400, but were then forced to use a potentiometric titration method. Roland3 used 75 per cent. ethanol in water and titrated the salts potentiometrically with 0.1N hydrochloric acid. He deplored the use of indicators and stated that in his opinion they were not accurate. This, of course, is understandable for such weak acids in a system containing 25 per cent. water.Vespe and Fritz4 titrated barbituric acids in dimethylformamide as solvent and their investigation was confirmed and expanded by Ryan, Yanowski and Pifer6. It was noted in this laboratory, however, that the end-point in such a system faded rapidly even when the titration flask was protected carefully from the atmosphere. It was noted, furthermore, that when using this solvent, there was a distinct tendency to overestimate the barbiturate content of certain coloured tablet preparations. In addition, dimethylformamide is unpleasant to work with and constitutes an actual danger to the respiratory system.The main objection to the methods employed by other workersl~~*~ was that the titration could be carried out only potentiometrically. It was decided, therefore, to seek a solvent system which did not possess the disadvantages that are inherent in dirnethylformamide, but which yet permitted a visual titration of the barbiturates.For the titration of weak acids in nonaqueous solvents, most workers have employed a methoxide titrant which is prepared with either metallic sodium, potassium or lithium. A recent publication by Crisafio and Chatten6 has shown that a 0.1N solution of potassium hydroxide in anhydrous methanol was equally satisfactory for the titration of the bile acids and was much simpler to prepare than the conventional methoxides. Caldin and Long' proved that, in reality, a solution of sodium hydroxide in methanol did not differ in methoxide content from one prepared by using metallic sodium. It would appear reasonable to extend their findings on sodium hydroxide to include potassium hydroxide. 504