A study of folic acid stability in solutions of the B complex vitamins


  • Presented at the joint session of the Subsection on Pharmacy, American Association for the Advancement of Science and the American Pharmaceutical Association, Scientific Section, Cleveland, Ohio, December 29, 1950.


The stability of folic acid was studied at pH values between 3 and 7 in liquid media containing, individually and conjointly, the following members of the vitamin B complex: thiamine hydrochloride, riboflavin, nicotinamide, pyridoxine, and panto-thenyl alcohol. At the lower pH levels where water or sucrose syrup was used as vehicle, the folic acid was largely undissolved, whereas at the higher pH levels, the folic acid in the concentration used was completely dissolved. In a mixture of propylene glycol and water, the folic acid was completely dissolved throughout the entire pH range. Data are presented on the aomount of folic acid decomposition after storage at room temperature and also at 45. In eneral, riboflavin and thiamine caused considerable decomposition of folk acif in solution. Specimens at the lower pH levels where the folic acid was for the most part undissolved exhibited a stability which might be practical for pharmaceutical compounding purposes. Nicotinamide, pyridoxine, and pantothenyl alcohol did not materially affect the stability of folic acid in solution. Data are also presented on the solubility of folic acid in water as a function of pH and of temperature, and on the stability of folic acid in aqueous media as a function of pH. The decomposition of folic acid in the presence of riboflavin and thiamine involves cleavage at the methylene linkage, liberating an aromatic amine, presumably p-aminobenzoylglutamic acid. This is analogous to the reaction which takes place upon the acid reduction of folic acid as is used in the chemical determination of this substance.