Detection of Urinary Drug Metabolite (Xenometabolome) Signatures in Molecular Epidemiology Studies via Statistical Total Correlation (NMR) Spectroscopy

Abstract

Western populations use prescription and nonprescription drugs extensively, but large-scale population usage is rarely assessed objectively in epidemiological studies. Here we apply statistical methods to characterize structural pathway connectivities of metabolites of commonly used drugs detected routinely in 1H NMR spectra of urine in a human population study. 1H NMR spectra were measured for two groups of urine samples obtained from U.S. participants in a known population study. The novel application of a statistical total correlation spectroscopy (STOCSY) approach enabled rapid identification of the major and certain minor drug metabolites in common use in the population, in particular, from acetaminophen and ibuprofen metabolites. This work shows that statistical connectivities between drug metabolites can be established in routine “high-throughput” NMR screening of human samples from participants who have randomly self-administered drugs. This approach should be of value in considering interpopulation patterns of drug metabolism in epidemiological and pharmacogenetic studies.

Metabolomic Pattern Analysis after Mediterranean Diet Intervention in a Nondiabetic Population: A 1- and 3-Year Follow-up in the PREDIMED Study

“…To allow differentiation of spectra without the overriding influence of the strong acetaminophen peaks, these signals from the NMR data were removed before performing further metabolomic analysis (38). Then, the OSC-PLS-DA analysis resulted in a model with R 2 Y=0.75 and Q 2 = 0.58.…”

Analytic Properties of Statistical Total Correlation Spectroscopy Based Information Recovery in 1H NMR Metabolic Data Sets

“…There are now numerous applications of STOCSY and closely related covariance techniques for enhanced information recovery from low dimensional NMR data sets on multiple and single samples [3][4][5][6][7][8][9][10][11][12][13] . The STOCSY approach has been applied to the structural assignment problem in a variety of NMR metabolic profiling contexts, such as deconvolution of overlapped chromatographic peaks in LC-NMR 7 , delineation of drug metabolism in molecular epidemiology studies 5 and separation of different molecular signatures in diffusion edited spectroscopy 6 .…”

Urinary metabolomic fingerprinting after consumption of a probiotic strain in women with mastitis

“…These pharmacological drugs are widely used in the amelioration of mastitis pain [2,29]. Additionally, acetaminophen, ibuprofen and their related metabolites are readily identifiable in 1 H-NMR urine spectra, and their spectral signatures are distinctive in human urinary metabolome after their ingestion [25,30].…”

“…Metabolites from acetaminophen and ibuprofen not available in such libraries and databases are identified by bibliographic support [25,26]. Further, Pearson's correlation test was performed to assess correlations between signals corresponding to the same metabolite.…”