Large-scale human metabolic phenotyping and molecular epidemiological studies via 1H NMR spectroscopy of urine: investigation of borate preservation.

Borate is an antibacterial preservative widely used in clinical and large-scale epidemiological studies involving urine sample analysis. Since it readily forms covalent adducts and reversible complexes with hydroxyl and carboxylate groups, the effects of borate preservation in 1H NMR-spectroscopy-based metabolic profiling of human urine samples have been assessed. Effects of various concentrations of borate (range 0−30 mM) on 1H NMR spectra of urine were observed at sequential time points over a 12 month period. Consistent with known borate chemistry, the principal alterations in the 1H resonance metabolite patterns were observed for compounds such as mannitol, citrate, and α-hydroxyisobutyrate and confirmed by ESI-MS analysis. These included line-broadening, T1 and T2 relaxation, and chemical shift changes consistent with complex formation and chemical exchange processes. To further investigate complexation behavior in the urinary metabolite profiles, a new tool for visualization of multicomponent relaxa...