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

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 silica-lactose samples, and lower amounts of trace paramagnetic contaminants in highly diluted silica-lactose samples, which could provide a clue.