Precipitation of calcium gluceptate from aqueous solutions

A precipitate encountered in solutions of calcium gluceptate was identified as hydrated calcium gluceptate. Precipitation was associated with a change from a very soluble amorphous anhydrous form to a sparingly soluble crystalline hydrate, the presence of seed crystals inducing crystallization, and unsuitable proportions of the α‐ and β‐epimers of calcium gluceptate. Various commercial samples and the corresponding precipitates were examined by elemental analysis, thermal analysis, X‐ray diffraction, IR spectroscopy, and GC‐MS. The proportion of the α‐ and β‐epimers in commercial samples was quantitated by GC. In this method, an aqueous solution of calcium gluceptate was converted into a mixture of glucoheptonic acids and their corresponding lactones by passage through a cation‐exchange resin. The solution was freeze‐dried, the acid‐lactone mixture converted to the γ‐lactones using concentrated hydrochloric acid, and the resulting material trimethylsilylated with trimethylsilylimidazole. Stability studies of solutions prepared from calcium gluceptate obtained from various commercial sources indicate that above ˜50% α‐epimer, stability decreased with an increase in the relative proportion of the α‐epimer. Material complying with USP specifications (pure α‐epimer) is the least stable in solution. It is suggested that calcium gluceptate containing approximately equal proportions of the α‐ and β‐epimers be introduced in the USP monograph together with a method for estimating the proportions of the epimers.