title: 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.
authors.affiliation: Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics (SORA), Faculty of Medicine, Imperial College London, SW7 2AZ, UK.
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
authors.forename: Ruey Leng
authors.initials: RL
authors.lastname: Loo
authors.forename: Olivier
authors.initials: O
authors.lastname: Cloarec
authors.forename: Muireann
authors.initials: M
authors.lastname: Coen
authors.forename: Huiru
authors.initials: H
authors.lastname: Tang
authors.forename: Elaine
authors.initials: E
authors.lastname: Maibaum
authors.forename: Stephen
authors.initials: S
authors.lastname: Bruce
authors.forename: Queenie
authors.initials: Q
authors.lastname: Chan
authors.forename: Paul
authors.initials: P
authors.lastname: Elliott
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Stamler
authors.forename: Ian D
authors.initials: ID
authors.lastname: Wilson
authors.forename: John C
authors.initials: JC
authors.lastname: Lindon
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
mesh_terms: D000082:Acetaminophen / Q000737:chemistry / Q000378:metabolism / Q000652:urine*; D006801:Humans; D007052:Ibuprofen / Q000737:chemistry / Q000378:metabolism / Q000652:urine*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods* / Q000706:statistics & numerical data*; D053858:Metabolic Networks and Pathways; D015394:Molecular Structure; D015999:Multivariate Analysis; D044469:Racial Groups; D012680:Sensitivity and Specificity; D014481:United States / Q000453:epidemiology
chemical_list: D000082:Acetaminophen; D007052:Ibuprofen