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

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• 作者：Elaine Holmes ; Ruey Leng Loo ; Olivier Cloarec ; Muireann Coen ; Huiru Tang ; Elaine Maibaum ; Stephen Bruce ; Queenie Chan ; Paul Elliott ; Jeremiah Stamler ; Ian D. Wilson ; John C. Lindon ; Jeremy K. Nicholson
• 刊名：Analytical Chemistry
• 出版年：2007
• 出版时间：April 1, 2007
• 年：2007
• 卷：79
• 期：7
• 页码：2629 - 2640
• 全文大小：490K
• 年卷期：v.79,no.7(April 1, 2007)
• ISSN：1520-6882

文摘

Western populations use prescription and nonprescription drugs extensively, but large-scale population usageis rarely assessed objectively in epidemiological studies.Here we apply statistical methods to characterize structural pathway connectivities of metabolites of commonlyused drugs detected routinely in ¹H NMR spectra of urinein a human population study. ¹H NMR spectra weremeasured for two groups of urine samples obtained fromU.S. participants in a known population study. The novelapplication of a statistical total correlation spectroscopy(STOCSY) approach enabled rapid identification of themajor and certain minor drug metabolites in common usein the population, in particular, from acetaminophen andibuprofen metabolites. This work shows that statisticalconnectivities between drug metabolites can be established in routine "high-throughput" NMR screening ofhuman samples from participants who have randomly self-administered drugs. This approach should be of value inconsidering interpopulation patterns of drug metabolismin epidemiological and pharmacogenetic studies.