The Effect of Alkalis Upon the Solubility of Quinine Salts.

The present study was suggested by the paper by Eggleston 1 pointing out the need for further experimental data concerning factors influencing the absorption of drugs from the gastro-intestinal tract. The literature reveals a surprising dearth of material, particularly as relating to the rôle of hydrogen ion concentration as a factor in absorption.

The immediate problem was the determination of the solubility of soluble quinine salts (hydrochloride, dihydrochloride and bisulphate) in solutions of various alkaline salts at various concentrations and pH, when equal parts of 2% quinine salt and alkaline salt were mixed. The alkaline salts employed were K₂HPO₄, Na acetate, Na citrate, NaHCO₃ and Na₂CO₃. The effect of OH ion was learned through the use of NaOH. An end concentration of 1% quinine salt was thought to approximate the expected concentration in the stomach and duodenum after a full therapeutic dose of quinine. The pH determinations were made colorimetrically, using the Michaelis 2 one-color series without buffers, and these values checked by the quinhydrone electrode.

As shown in the table, the average precipitation point of the hydrochloride is at a pH of 7.19, the dihydrochloride 3.62, and the bisulphate 3.46. It will be noted that these values are in almost the same relation as the pH values of their aqueous solutions. A 2% solution of quinine hydrochloride was found to have a pH of 6.1, dihydrochloride 2.6 and bisulphate 2.4. It will be also noted that the pH figures all lie within the pH ranges of the human stomach and duodenum, as reported by McClendon, 3 Hume, Denis, Silverman and Irwin, 4 and others.

Qualitative determinations on the precipitates showed that they were quinine salts corresponding with the precipitating alkaline salt, viz., quinine acetate, phosphate, carbonate, etc. With NaOH the preciptate was quinine base. The process was apparently stoechio-metric.