{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,13]],"date-time":"2026-09-13T05:04:55Z","timestamp":1789275895355,"version":"build-2803163510"},"reference-count":51,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T00:00:00Z","timestamp":1789084800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Grants-in-Aid for Scientific Research in Priority Areas of Cancer","award":["17015018"],"award-info":[{"award-number":["17015018"]}]},{"name":"Innovative Areas","award":["221S0001"],"award-info":[{"award-number":["221S0001"]}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16H06277"],"award-info":[{"award-number":["16H06277"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22H04923"],"award-info":[{"award-number":["22H04923"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["22K06706"],"award-info":[{"award-number":["22K06706"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"award":["16H06277"],"award-info":[{"award-number":["16H06277"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]},{"award":["22H04923"],"award-info":[{"award-number":["22H04923"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]},{"award":["22K06706"],"award-info":[{"award-number":["22K06706"]}],"id":[{"id":"https:\/\/ror.org\/00hhkn466","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009619","name":"Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/004rtk039","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Background\/Objectives: Cytochrome P450(CYP)2C19 activity varies widely among individuals. As genetic factors, CYP2C19*2 and CYP2C19*3 alleles reduce CYP2C19 activity, while the CYP2C19*17 allele increases CYP2C19 activity. However, environmental and physiological factors can also influence individual CYP2C19 activity. In this study, we searched for novel endogenous biomarkers for CYP2C19 activity using CYP2C19 gene polymorphism data combined with results of untargeted metabolomic analysis. Methods: 431 general adults analyzed in the Kyoto J-MICC Study and 255 patients who visited Oita University Hospital were studied. Plasma samples were pretreated by solid-phase and liquid-liquid extraction and subjected to untargeted metabolomic analysis using ultra-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. Based on CYP2C19 gene polymorphism data, participants were classified into extensive metabolizers (EM), intermediate metabolizers (IM), and poor metabolizers (PM). Compounds showing significant differences in abundance among the three groups were considered candidate compounds for predicting CYP2C19 activity. The predictive performance of candidate compounds for CYP2C19 PM status was evaluated using covariate-adjusted receiver operating characteristic (ROC) analysis. Results: The normalized abundance of compounds with m\/z 160.1342, 303.2319 (a fatty acyl or prenol lipid), 314.2309, 449.3238, 653.3021, 792.5744, and 811.5988 (a glycerophospholipid or sphingolipid), and 902.5404 (a fatty acyl) differed significantly among CYP2C19 EM, IM, and PM groups (p &lt; 0.05), and these eight compounds were considered candidate compounds. Covariate-adjusted ROC analysis showed that none of the candidate compounds significantly improved the discrimination of CYP2C19 PM status. Conclusions: Untargeted metabolomics combined with CYP2C19 gene polymorphism data yielded eight compounds associated with CYP2C19 phenotype. Further studies are needed to evaluate the usefulness of these compounds as biomarkers of CYP2C19 activity.<\/jats:p>","DOI":"10.3390\/metabo16090670","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T10:51:37Z","timestamp":1789123897000},"page":"670","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Search for Novel Biomarkers to Predict Cytochrome P450 2C19 Activity Using Untargeted Metabolomics of Human Plasma"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-1423-5622","authenticated-orcid":false,"given":"Ayako","family":"Oda","sequence":"first","affiliation":[{"name":"Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose 204-8588, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Yosuke","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose 204-8588, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8161-368X","authenticated-orcid":false,"given":"Teruhide","family":"Koyama","sequence":"additional","affiliation":[{"name":"Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan"},{"name":"Faculty of Regional Creation, Nara Prefectural University, 10 Funabashi-cho, Nara City 630-8258, Nara, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Jun","family":"Negami","sequence":"additional","affiliation":[{"name":"Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose 204-8588, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Sakura","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose 204-8588, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Koudai","family":"Iino","sequence":"additional","affiliation":[{"name":"Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose 204-8588, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Nao","family":"Yamagishi","sequence":"additional","affiliation":[{"name":"Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose 204-8588, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Natsuki","family":"Kamio","sequence":"additional","affiliation":[{"name":"Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose 204-8588, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1225-8303","authenticated-orcid":false,"given":"Etsuko","family":"Ozaki","sequence":"additional","affiliation":[{"name":"Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan"},{"name":"Department of Nursing Faculty of Health and Medical Sciences, Kyoto University of Advanced Science, 18 Gotanda-cho, Yamanouchi, Ukyo-ku, Kyoto 615-8577, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6922-4835","authenticated-orcid":false,"given":"Yasuyuki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1838-4837","authenticated-orcid":false,"given":"Masahiro","family":"Nakatochi","sequence":"additional","affiliation":[{"name":"Public Health Informatics Unit, Department of Integrated Health Sciences, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Yukihide","family":"Momozawa","sequence":"additional","affiliation":[{"name":"Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Kanagawa, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8452-7971","authenticated-orcid":false,"given":"Ryota","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Oita University Hospital, 1-1 Idaigaoka, Hasama-machi, Yufu 879-5593, Oita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]},{"given":"Hiroyuki","family":"Ono","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Oita University Hospital, 1-1 Idaigaoka, Hasama-machi, Yufu 879-5593, Oita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"given":"Takahiro","family":"Sumimoto","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Oita University Hospital, 1-1 Idaigaoka, Hasama-machi, Yufu 879-5593, Oita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4949-362X","authenticated-orcid":false,"given":"Ryosuke","family":"Tatsuta","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Oita University Hospital, 1-1 Idaigaoka, Hasama-machi, Yufu 879-5593, Oita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0322-9356","authenticated-orcid":false,"given":"Hiroki","family":"Itoh","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacy, Oita University Hospital, 1-1 Idaigaoka, Hasama-machi, Yufu 879-5593, Oita, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Naoyuki","family":"Takashima","sequence":"additional","affiliation":[{"name":"Department of Epidemiology for Community Health and Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1761-6314","authenticated-orcid":false,"given":"Keitaro","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Division of Cancer Epidemiology and Prevention, Aichi Cancer Center, 1-1 Kanokoden, Chigusa-ku, Nagoya 464-8681, Aichi, Japan"},{"name":"Department of Cancer Epidemiology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, Aichi, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"}]},{"given":"Keiko","family":"Ohno","sequence":"additional","affiliation":[{"name":"Department of Medication Use Analysis and Clinical Research, Meiji Pharmaceutical University, 2-522-1 Noshio, Kiyose 204-8588, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/S0090-9556(25)08409-0","article-title":"Human CYP2C19 is a major omeprazole 5-hydroxylase, as demonstrated with recombinant cytochrome P450 enzymes","volume":"24","author":"Karam","year":"1996","journal-title":"Drug Metab. Dispos."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1124\/dmd.109.029132","article-title":"Identification of the human cytochrome P450 enzymes involved in the two oxidative steps in the bioactivation of clopidogrel to its pharmacologically active metabolite","volume":"38","author":"Kazui","year":"2010","journal-title":"Drug Metab. Dispos."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1124\/dmd.122.000829","article-title":"The pharmacokinetics, metabolism, and clearance mechanisms of abrocitinib, a selective Janus kinase inhibitor, in humans","volume":"50","author":"Bauman","year":"2022","journal-title":"Drug Metab. Dispos."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"15419","DOI":"10.1016\/S0021-9258(17)40694-6","article-title":"The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans","volume":"269","author":"Wilkinson","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1016\/S0026-895X(25)09788-3","article-title":"Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese","volume":"46","author":"Wilkinson","year":"1994","journal-title":"Mol. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.clpt.2005.10.002","article-title":"A common novel CYP2C19 gene variant causes ultrarapid drug metabolism relevant for the drug response to proton pump inhibitors and antidepressants","volume":"79","author":"Sim","year":"2006","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1111\/j.1365-2125.2007.03057.x","article-title":"Limited frequency of the CYP2C19*17 allele and its minor role in a Japanese population","volume":"65","author":"Sugimoto","year":"2008","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"959","DOI":"10.1002\/cpt.2526","article-title":"Clinical pharmacogenetics implementation consortium guideline for CYP2C19 genotype and clopidogrel therapy: 2022 Update","volume":"112","author":"Lee","year":"2022","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1519","DOI":"10.1007\/s40262-022-01173-8","article-title":"The cytokine release syndrome and\/or the proinflammatory cytokines as underlying mechanisms of downregulation of drug metabolism and drug transport: A systematic review of the clinical pharmacokinetics of victim drugs of this drug-disease interaction under different clinical conditions","volume":"61","author":"Gatti","year":"2022","journal-title":"Clin. Pharmacokinet."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1177\/0091270005280787","article-title":"In vivo metabolic activity of CYP2C19 and CYP3A in relation to CYP2C19 genetic polymorphism in chronic liver disease","volume":"45","author":"Ohnishi","year":"2005","journal-title":"J. Clin. Pharmacol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1007\/s43440-020-00127-w","article-title":"End-stage renal disease reduces the expression of drug-metabolizing cytochrome P450s","volume":"72","author":"Deri","year":"2020","journal-title":"Pharmacol. Rep."},{"key":"ref_12","unstructured":"European Medicines Agency (2025, June 15). Guideline on the Investigation of Drug Interactions-Revision 1. 6 July 2012. Updated 3 June 2015, Available online: https:\/\/www.ema.europa.eu\/en\/investigation-drug-interactions-scientific-guideline."},{"key":"ref_13","unstructured":"US Food and Drug Administration (2025, June 15). Drug Development and Drug Interactions. Table of Substrates, Inhibitors and Inducers, Available online: https:\/\/www.fda.gov\/drugs\/drug-interactions-labeling\/drug-development-and-drug-interactions-table-substrates-inhibitors-and-inducers#table2-1."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.2147\/DDDT.S131797","article-title":"Drug-drug interaction of microdose and regular-dose omeprazole with a CYP2C19 inhibitor and inducer","volume":"11","author":"Park","year":"2017","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1007\/s00228-022-03304-3","article-title":"Evaluation of CYP2C19 activity using microdosed oral omeprazole in humans","volume":"78","author":"Elbe","year":"2022","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1007\/s13318-024-00896-2","article-title":"The use of microdosing for in vivo phenotyping of cytochrome P450 enzymes: Where do we stand? a narrative review","volume":"49","author":"Opdam","year":"2024","journal-title":"Eur. J. Drug Metab. Pharmacokinet."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1373","DOI":"10.1007\/s40262-019-00783-z","article-title":"Phenotyping of human CYP450 enzymes by endobiotics: Current knowledge and methodological approaches","volume":"58","author":"Magliocco","year":"2019","journal-title":"Clin. Pharmacokinet."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1002\/mas.21548","article-title":"Metabolomics toward personalized medicine","volume":"38","author":"Jacob","year":"2019","journal-title":"Mass Spectrom. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Yeung, P.K. (2018). Metabolomics and biomarkers for drug discovery. Metabolites, 8.","DOI":"10.3390\/metabo8010011"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4708","DOI":"10.1111\/bph.15651","article-title":"Metabolomics reveals biomarkers in human urine and plasma to predict cytochrome P450 2D6 (CYP2D6) activity","volume":"178","author":"Magliocco","year":"2021","journal-title":"Br. J. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1186\/s40246-024-00579-8","article-title":"Solanidine is a sensitive and specific dietary biomarker for CYP2D6 activity","volume":"18","author":"Kiiski","year":"2024","journal-title":"Hum. Genom."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1002\/cpt.856","article-title":"Identification of omega- or (omega-1)-Hydroxylated Medium-Chain Acylcarnitines as Novel Urinary Biomarkers for CYP3A Activity","volume":"103","author":"Kim","year":"2018","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_23","first-page":"317","article-title":"The Japan Multi-Institutional Collaborative Cohort Study (J-MICC Study) to detect gene-environment interactions for cancer","volume":"8","author":"Hamajima","year":"2007","journal-title":"Asian Pac. J. Cancer Prev."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"223","DOI":"10.2188\/jea.JE20100139","article-title":"Profile of participants and genotype distributions of 108 polymorphisms in a cross-sectional study of associations of genotypes with lifestyle and clinical factors: A project in the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study","volume":"21","author":"Wakai","year":"2011","journal-title":"J. Epidemiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"660","DOI":"10.2188\/jea.JE20200147","article-title":"Study profile of the Japan Multi-institutional Collaborative Cohort (J-MICC) Study","volume":"31","author":"Takeuchi","year":"2021","journal-title":"J. Epidemiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"982","DOI":"10.1053\/j.ajkd.2008.12.034","article-title":"Revised equations for estimated GFR from serum creatinine in Japan","volume":"53","author":"Matsuo","year":"2009","journal-title":"Am. J. Kidney Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.5551\/jat.41517","article-title":"Genetic variants of RAMP2 and CLR are associated with stroke","volume":"24","author":"Koyama","year":"2017","journal-title":"J. Atheroscler. Thromb."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1704","DOI":"10.1056\/NEJMoa1008410","article-title":"Effects of CYP2C19 genotype on outcomes of clopidogrel treatment","volume":"363","author":"Pare","year":"2010","journal-title":"N. Engl. J. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1007\/s11096-013-9783-y","article-title":"CYP2C19 genotypes and their impact on clopidogrel responsiveness in percutaneous coronary intervention","volume":"35","author":"Mejin","year":"2013","journal-title":"Int. J. Clin. Pharm."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1097\/FPC.0b013e3283349e84","article-title":"Cytochrome P450 2C9-CYP2C9","volume":"20","author":"Marsh","year":"2010","journal-title":"Pharmacogenet. Genom."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1038\/nmeth.2307","article-title":"Improved whole-chromosome phasing for disease and population genetic studies","volume":"10","author":"Delaneau","year":"2013","journal-title":"Nat. Methods"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1038\/ng.3656","article-title":"Next-generation genotype imputation service and methods","volume":"48","author":"Das","year":"2016","journal-title":"Nat. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"Auton","year":"2015","journal-title":"Nature"},{"key":"ref_34","unstructured":"Nonlinear Dynamics Website (2025, December 04). How Does Progenesis Correct for Drifts in Retention Time?. Available online: https:\/\/www.nonlinear.com\/progenesis\/qi\/v2.0\/faq\/how-alignment-works.aspx."},{"key":"ref_35","unstructured":"Nonlinear Dynamics Website (2025, December 04). How Does Normalisation Work in Progenesis QI?. Available online: https:\/\/www.nonlinear.com\/progenesis\/qi\/v2.0\/faq\/how-normalisation-works.aspx."},{"key":"ref_36","unstructured":"Nonlinear Dynamics Website (2025, December 04). How Are the Compound Ions Grouped into Compounds?. Available online: https:\/\/www.nonlinear.com\/progenesis\/qi\/v2.0\/faq\/how-does-deconvolution-work.aspx."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2589","DOI":"10.1039\/C3MB70194H","article-title":"Trials and tribulations of \u2018omics data analysis: Assessing quality of SIMCA-based multivariate models using examples from pulmonary medicine","volume":"9","author":"Wheelock","year":"2013","journal-title":"Mol. Biosyst."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"743","DOI":"10.1038\/nprot.2011.319","article-title":"Web-based inference of biological patterns, functions and pathways from metabolomic data using MetaboAnalyst","volume":"6","author":"Xia","year":"2011","journal-title":"Nat. Protoc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s11306-007-0082-2","article-title":"Proposed minimum reporting standards for chemical analysis Chemical Analysis Working Group (CAWG) Metabolomics Standards Initiative (MSI)","volume":"3","author":"Sumner","year":"2007","journal-title":"Metabolomics"},{"key":"ref_40","unstructured":"(2025, June 15). Metabolite Structures. Available online: https:\/\/www.hmdb.ca\/downloads."},{"key":"ref_41","unstructured":"LipidBlast (2025, June 15). LipidBlast Full Release 3. Zip. Available online: https:\/\/www.nonlinear.com\/progenesis\/qi\/v2.3\/faq\/how-do-i-configure-the-lipidblast-databases-without-internet-access.aspx."},{"key":"ref_42","unstructured":"Nonlinear Dynamics Website (2025, December 04). How Are the Scores Calculated for Possible Compound Identifications?. Available online: https:\/\/www.nonlinear.com\/progenesis\/qi\/v3.0\/faq\/identifications-scoring-algorithm.aspx."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"116","DOI":"10.1016\/j.abb.2008.01.002","article-title":"Metabolism of eicosapentaenoic and docosahexaenoic acids by recombinant human cytochromes P450","volume":"471","author":"Fer","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Chen, L., Zhong, F., and Zhu, J. (2020). Bridging Targeted and untargeted mass spectrometry-based metabolomics via hybrid approaches. Metabolites, 10.","DOI":"10.3390\/metabo10090348"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.2217\/pgs.14.155","article-title":"Detection of an endogenous urinary biomarker associated with CYP2D6 activity using global metabolomics","volume":"15","author":"Shireman","year":"2014","journal-title":"Pharmacogenomics"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1342","DOI":"10.1124\/dmd.122.000957","article-title":"Isolation and identification of 3,4-seco-solanidine-3,4-dioic acid (SSDA) as a urinary biomarker of cytochrome P450 2D6 (CYP2D6) activity","volume":"50","author":"Behrle","year":"2022","journal-title":"Drug Metab. Dispos."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1111\/j.1651-2227.2006.00178.x","article-title":"Understanding diagnostic tests 3: Receiver operating characteristic curves","volume":"96","author":"Akobeng","year":"2007","journal-title":"Acta Paediatr."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1007\/s00228-023-03462-y","article-title":"Prediction of CYP2D6 poor metabolizers by measurements of solanidine and metabolites-a study in 839 patients with known CYP2D6 genotype","volume":"79","author":"Wollmann","year":"2023","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1002\/cpt.3106","article-title":"Nutrimetric validation of solanidine as dietary-derived CYP2D6 activity marker in vivo","volume":"115","author":"Muller","year":"2024","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"740","DOI":"10.1111\/bcp.15721","article-title":"Evidence for solanidine as a dietary CYP2D6 biomarker: Significant correlation with risperidone metabolism","volume":"90","author":"Wollmann","year":"2024","journal-title":"Br. J. Clin. Pharmacol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1269","DOI":"10.1002\/cpt.3380","article-title":"Solanidine metabolites as diet-derived biomarkers of CYP2D6-mediated tamoxifen metabolism in breast cancer patients","volume":"116","author":"Medwid","year":"2024","journal-title":"Clin. Pharmacol. 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