Low-field NMR water proton longitudinal relaxation in ultrahighly diluted aqueous solutions of silica-lactose prepared in glass material for pharmaceutical use

Abstract

Low-field (0.02–4 MHz) proton nuclear magnetic resonance (NMR) longitudinal relaxometry was applied to ultrahighly diluted aqueous solutions in order to detect physical modifications induced in the solvent by the dilution process. A mixture of silica-lactose (1.67·10⁻⁵ M silica, 2.92·10⁻² M lactose) was initially solubilized in water or in saline, then submitted to eighteen iterative centesimal dilutions in water or in saline under vigorous vortex agitation and rigorously controlled atmospheric conditions, and compared to similarly treated pure water and saline as controls. Several independent series of samples were measured according to a blind protocol (total of 140 code-labelled samples). A slight frequency dispersion (about 4%) was found within the 0.02–4 MHz range, centered around 0.55 MHz, and ascribed to combined effects of silica and trace paramagnetic contaminants, both concentrated and in a reduced motion at the borosilicate wall tube interface. The iterative dilution-agitation process in pure water and saline induced no significant effect on relaxivity. Slightly increased relaxivity compared to solvent was found in the initial silica-lactose dilution (especially in saline, about 4%), which vanished unexpectedly slowly upon dilution, as adjusted to an arbitrary log-linear model. Statistical analysis was applied to succeed in discriminating solutions from their solvents beyond the 10⁻¹² level of dilution. No clear explanation emerged, but post-experiment chemical analysis revealed high amounts (6 ppm) of released silica from the glass material used, with excess in silicalactose samples, and lower amounts of trace paramagnetic contaminants in highly diluted silica-lactose samples, which could provide a clue.