Use of high-resolution proton nuclear magnetic resonance spectroscopy for rapid multi-component analysis of urine.

Abstract

Numerous low-Mr metabolites--including creatinine, citrate, hippurate, glucose, ketone bodies, and various amino acids--have been identified in 400- and 500-MHz proton nuclear magnetic resonance (1H NMR) spectra of intact human urine. The presence of many of these was related to the specific condition of the donors: humans in different physiological states (resting, fasting, or post-exercise) and pathological conditions (e.g., diabetes mellitus, cadmium-induced renal dysfunction). We have also monitored the metabolism of simple nonendogenous compounds (methanol and ethanol) and of acetaminophen. The pH-dependencies of the NMR chemical shifts of some urine components are reported. Our studies show that high-resolution 1H NMR spectroscopy provides a fast, simple method for "fingerprint" identification of urinary compounds. In some cases, analytes can be quantified by standard additions or by comparing integrated peak areas for the metabolites with those for creatinine. Determinations of creatinine by 1H NMR spectroscopy compared well with those by an independent chemical assay based on the Jaffé reaction.

High‐Resolution Proton Magnetic Resonance Analysis of Human Cerebrospinal Fluid

“…Phenytoin had been stopped and all medications switched to a nonintravenous route on day 15, well before the second specimen illustrated. Figure 1 shows a representative 500 MHz 'H NMR spectrum of CSF from patient A. Resonance assignments were made on the basis of pure compound spectra obtained in our buffer system (Behar et al, 1983) and literature values (Bock, 1982;Bales et al, 1984;Bolinger et al, 1984). Resonances assigned in this way included glucose, lactate (1.33 and 4.12 ppm), glutamine (2.14,2.46, 3.78 ppm), citrate (2.53 and 2.69 ppm), acetate (1.92 ppm), creatine (3.04 ppm), creatinine (3.06 ppm), alanine (1.49 and 3.78 ppm), and p-hydroxybutyrate ( 1.2 1, 2.3 1, 2.42, 4.13 ppm).…”

“…Its first application in the study of body fluids was to analyze human milk (Odeblad and Westin, 1958). More recently, high-resolution 'H NMR has been used to analyze blood, serum, plasma (Bock, 1982;Nicholson et al, 1983Nicholson et al, , 1984Traube et al, 1983), urine (Bales et al, 1984;Nicholson et al, 1984;Iles et al, 1984), amniotic fluid (Gillies et al, 1985), and CSF (Bhacca et al, 1985;Bales et al, 1985;Petroff et al, 19853) of patients with various clinical problems. We report here our further analyses of human CSF using this powerful technique.…”

The Current Status of Metabolomics in Drug Discovery and Development

“…Early work utilizing NMR spectroscopy to study biofluids [Nicholson et al, 1983;Bales et al, 1984] recognized the extremely rich and easily obtainable information contained in a simple high-field proton NMR spectrum. In the intervening decades, advancements in NMR technology have empowered the method further as a tool for analyzing whole biological fluids and tissues [Nicholson et al, 2002;Dunn et al, 2011].…”

High resolution proton NMR spectroscopy of human amniotic fluid

“…Nuclear magnetic resonance (NMR) is ideally suited to characterize the complex chemical composition of HAF. NMR spectroscopy has been used to study plasma (Bock, 1982;Nicholson el al., 1983Nicholson el al., , 1984aBales et al, 1984), and urine (Nicholson et al 1984b;Lehnert, 1986). Many of the critical compounds already implicated with fetal developmental abnormalities are identifiable by NMR spectroscopy.…”