POLARIMETRIC RESEARCH OF PHARMACEUTICAL SUBSTANCES IN AQUEOUS SOLUTIONS WITH DIFFERENT WATER ISOTOPOLOGUES RATIO
Objective: Methodology development for quality control of optically active pharmaceutical substances based on water isotopologues.
Methods: Solutions of L-ascorbic acid, glucose, galactose and valine stereoisomers were prepared using deuterium depleted water (DDW-Â«lightÂ» water, D/H=4 ppm), natural deionized high-ohmic water (BD, D/H=140 ppm), heavy water (99.9% D2O). The optical rotation was observed using an automatic polarimeter Atago POL-1/2. The size distribution of giant heterogeneous clusters (GHC) of water was recorded by low angle laser light scattering (LALLS) method.
Results: The infringement of Biotâ€™s Law was found for solutions of ascorbic acid, expressed in the absence of a constant value of the specific optical rotation Â at a concentration of below 0.1%, depends on the D/H ratio. The inequality was established in absolute values of optical rotation for L-and D-isomers of valine in solutions with different ratios of hydrogen isotopologues. The mutarotation of glucose confirmed the first-order kinetics, and the activation energies were statistically distinguishable for BD and DDW. The mutarotation of the natural galactose D-isomer proceeded with a lower energy consumption compared to the L-isomer. In heavy water, the mutarotation of monosaccharides had different kinetic mechanisms. Polarimetric results correlated with the number and size of GHC, which confirmed the possibility of chiral solvent structures induction by optically active pharmaceutical substances.
Conclusion: In the optically active pharmaceutical substances quality control there should be considered the contribution of induced chiral GHC of water to the optical rotation value that depends on the isotopic D/H ratio, the substance nature and the form of its existence at a given pH.
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