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Information on dietary supplements, medications, and other xenobiotics in epidemiologic surveys is usually obtained from questionnaires and is subject to recall and reporting biases. The authors used metabolite data obtained from hydrogen-1 (or proton) nuclear magnetic resonance (1H NMR) analysis of human urine specimens from the International Study of Macro-/Micro-Nutrients and Blood Pressure (INTERMAP Study) to validate self-reported analgesic use. Metabolic profiling of two 24-hour urine specimens per individual was carried out for 4,630 participants aged 40–59 years from 17 population samples in Japan, China, the United Kingdom, and the United States (data collection, 1996–1999). 1H NMR-detected acetaminophen and ibuprofen use was low (∼4%) among East Asian population samples and higher (>16%) in Western population samples. In a comparison of self-reported acetaminophen and ibuprofen use with 1H NMR-detected acetaminophen and ibuprofen metabolites among 496 participants from Chicago, Illinois, and Belfast, Northern Ireland, the overall rate of concordance was 81%–84%; the rate of underreporting was 15%–17%; and the rate of underdetection was approximately 1%. Comparison of self-reported unspecified analgesic use with 1H NMR-detected acetaminophen and ibuprofen metabolites among 2,660 Western INTERMAP participants revealed similar levels of concordance and underreporting. Screening for urinary metabolites of acetaminophen and ibuprofen improved the accuracy of exposure information. This approach has the potential to reduce recall bias and other biases in epidemiologic studies for a range of substances, including pharmaceuticals, dietary supplements, and foods. [ABSTRACT FROM PUBLISHER]

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.