Abstract
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-«light» 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 Biot’s Law was found for solutions of ascorbic acid, expressed in the absence of a constant value of the specific optical rotation 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.
Highlights
Pharmacopoeias of different countries use the polarimetric method for identification and quantitative analysis of chiral active pharmaceutical ingredients (API) and excipients [1,2,3]
We demonstrated that the structure and size of water giant heterogeneous clusters (GHC) depend both on pH and on the isotopic composition of water, primarily on the ratio of deuterium: protium (D/H) [17]
In the non-linear function of specific optical rotation for 0.03-4 mol/l solutions of D-levoglucosan, the authors explain the presence of heterogeneous water structures, which sizes enlarge in case of dilution
Summary
Pharmacopoeias of different countries use the polarimetric method for identification and quantitative analysis of chiral active pharmaceutical ingredients (API) and excipients [1,2,3]. Pharmacopoeia measurements of the optical activity of API are carried out in waters with different pH values depending on the nature of the substance. For the purpose of quality control of carbohydrates, ammonia is added into the aqueous solution. This is accompanied by a change in the hydration conditions of monosaccharide molecules [10], and the equilibrium between α-and β-anomers is achieved in non-hourly, but minute kinetics [11]. Polarimetric analysis of amino acids is usually carried out in 6-8 mol/l HCl, where the amino acid is fully protonated (HOOC-X-NH3+) and optical rotation is constant [12]
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