title: Metabolic profiling and population screening of analgesic usage in nuclear magnetic resonance spectroscopy-based large-scale epidemiologic studies.
abstract: The application of a (1)H nuclear magnetic resonance (NMR) spectroscopy-based screening method for determining the use of two widely available analgesics (acetaminophen and ibuprofen) in epidemiologic studies has been investigated. We used samples and data from the cross-sectional INTERMAP Study involving participants from Japan (n = 1145), China (n = 839), U.K. (n = 501), and the U.S. (n = 2195). An orthogonal projection to latent structures discriminant analysis (OPLS-DA) algorithm with an incorporated Monte Carlo resampling function was applied to the NMR data set to determine which spectra contained analgesic metabolites. OPLS-DA preprocessing parameters (normalization, bin width, scaling, and input parameters) were assessed systematically to identify an optimal acetaminophen prediction model. Subsets of INTERMAP spectra were examined to verify and validate the presence/absence of acetaminophen/ibuprofen based on known chemical shift and coupling patterns. The optimized and validated acetaminophen model correctly predicted 98.2%, and the ibuprofen model correctly predicted 99.0% of the urine specimens containing these drug metabolites. The acetaminophen and ibuprofen models were subsequently used to predict the presence/absence of these drug metabolites for the remaining INTERMAP specimens. The acetaminophen model identified 415 out of 8436 spectra as containing acetaminophen metabolite signals while the ibuprofen model identified 245 out of 8604 spectra as containing ibuprofen metabolite signals from the global data set after excluding samples used to construct the prediction models. The NMR-based metabolic screening strategy provides a new objective approach for evaluation of self-reported medication data and is extendable to other aspects of population xenometabolome profiling.
authors.affiliation: Biomolecular Medicine, Division of Surgery, Oncology, Reproductive Biology and Anaesthetics, Faculty of Medicine, Imperial College London, SW7 2AZ, UK.
authors.forename: Ruey Leng
authors.initials: RL
authors.lastname: Loo
authors.forename: Muireann
authors.initials: M
authors.lastname: Coen
authors.forename: Timothy
authors.initials: T
authors.lastname: Ebbels
authors.forename: Olivier
authors.initials: O
authors.lastname: Cloarec
authors.forename: Elaine
authors.initials: E
authors.lastname: Maibaum
authors.forename: Magda
authors.initials: M
authors.lastname: Bictash
authors.forename: Ivan
authors.initials: I
authors.lastname: Yap
authors.forename: Paul
authors.initials: P
authors.lastname: Elliott
authors.forename: Jeremiah
authors.initials: J
authors.lastname: Stamler
authors.forename: Jeremy K
authors.initials: JK
authors.lastname: Nicholson
authors.forename: Elaine
authors.initials: E
authors.lastname: Holmes
mesh_terms: D000082:Acetaminophen / Q000627:therapeutic use / Q000652:urine*; D000328:Adult; D000700:Analgesics / Q000627:therapeutic use / Q000652:urine*; D016002:Discriminant Analysis; D016021:Epidemiologic Studies; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000627:therapeutic use / Q000652:urine*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D055442:Metabolome; D008875:Middle Aged; D011237:Predictive Value of Tests
chemical_list: D000700:Analgesics; D000082:Acetaminophen; D007052:Ibuprofen