{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T14:24:08Z","timestamp":1787408648445,"version":"build-2736575974"},"reference-count":51,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["ascpt.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Translational Sci"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The enzymatic activity of cytochrome P450 2D6 (CYP2D6) exhibits substantial interindividual variation, which influences drug efficacy and the risk of adverse drug reactions to various therapeutics. While current protocols for\n                    <jats:italic>CYP2D6<\/jats:italic>\n                    genotyping or CYP2D6 phenotyping provide useful information, less invasive and simpler tools are desirable for evaluating interindividual functional variety. Recently, solanidine (SND) and its metabolites have been proposed as biomarkers of CYP2D6 activity. In this study, we established a validated analytical method to quantify SND and its metabolites. Moreover, their utility in predicting CYP2D6 activity in the Japanese population was assessed. We synthesized and structurally confirmed 4\u2010hydroxysolanidine (4\u2010OHSND) and developed a liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS) method for the simultaneous measurement of SND, 4\u2010OHSND, and 3,4\u2010seco\u2010solanidine\u20103,4\u2010dioic acid (SSDA). This method was applied to plasma samples from 94 participants to investigate\n                    <jats:italic>the CYP2D6<\/jats:italic>\n                    genotypes. The 4\u2010OHSND to SND and SSDA to SND ratios showed substantial differences corresponding to the predicted CYP2D6 phenotype groups, with a marked reduction in poor metabolizers (PMs). Receiver operating characteristic analyses demonstrated complete discrimination of PMs (AUC\u2009=\u20091.00). In contrast, weak positive correlations were identified between SND biomarkers and certain tamoxifen metabolic ratios. These findings confirm the structural identity and quantitative detectability of 4\u2010OHSND and support its potential as a practical biomarker for CYP2D6 PM detection. Although validation in larger and more diverse cohorts remains necessary, diet\u2010derived biomarkers may represent a minimally invasive alternative to genotyping or probe\u2010based approaches and may contribute to the broad implementation of phenotype\u2010guided personalized medicine.\n                  <\/jats:p>","DOI":"10.1111\/cts.70668","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T08:52:00Z","timestamp":1784537520000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Liquid Chromatography\u2013Tandem Mass Spectrometry Quantification of Diet\u2010Derived\n                    <scp>CYP2D6<\/scp>\n                    Biomarkers for Clinical Phenotyping in Japanese Subjects"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2333-2847","authenticated-orcid":false,"given":"Masaki","family":"Kumondai","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences Tohoku University Hospital  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-6973-9996","authenticated-orcid":false,"given":"Nagomi","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8498-1341","authenticated-orcid":false,"given":"Yotaro","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Tohoku University Hospital  Sendai Japan"},{"name":"Faculty of Pharmaceutical Sciences Tohoku University  Sendai Japan"},{"name":"Laboratory of Oncology, Pharmacy Practice and Sciences, Graduate School of Pharmaceutical Sciences Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2420-6401","authenticated-orcid":false,"given":"Akiko","family":"Ebata","sequence":"additional","affiliation":[{"name":"Department of Breast and Endocrine Surgical Oncology, Graduate School of Medicine Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miku","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Breast and Endocrine Surgical Oncology, Graduate School of Medicine Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7001-0541","authenticated-orcid":false,"given":"Narumi","family":"Harada\u2010Shoji","sequence":"additional","affiliation":[{"name":"Department of Breast and Endocrine Surgical Oncology, Graduate School of Medicine Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Tada","sequence":"additional","affiliation":[{"name":"Department of Breast and Endocrine Surgical Oncology, Graduate School of Medicine Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4151-8725","authenticated-orcid":false,"given":"Minoru","family":"Miyashita","sequence":"additional","affiliation":[{"name":"Department of Breast and Endocrine Surgical Oncology, Graduate School of Medicine Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Ishida","sequence":"additional","affiliation":[{"name":"Department of Breast and Endocrine Surgical Oncology, Graduate School of Medicine Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6723-0298","authenticated-orcid":false,"given":"Masamitsu","family":"Maekawa","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Tohoku University Hospital  Sendai Japan"},{"name":"Faculty of Pharmaceutical Sciences Tohoku University  Sendai Japan"},{"name":"Laboratory of Biomolecule and Pathophysiological Chemistry, Graduate School of Pharmaceutical Sciences Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihisa","family":"Tomioka","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Tohoku University Hospital  Sendai Japan"},{"name":"Faculty of Pharmaceutical Sciences Tohoku University  Sendai Japan"},{"name":"Laboratory of Oncology, Pharmacy Practice and Sciences, Graduate School of Pharmaceutical Sciences Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1679-9024","authenticated-orcid":false,"given":"Nariyasu","family":"Mano","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Tohoku University Hospital  Sendai Japan"},{"name":"Faculty of Pharmaceutical Sciences Tohoku University  Sendai Japan"},{"name":"Laboratory of Biomolecule and Pathophysiological Chemistry, Graduate School of Pharmaceutical Sciences Tohoku University  Sendai Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharmthera.2012.12.007"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40262-019-00750-8"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1007"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2903"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3351"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1409"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.598"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.2149"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.597"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425255.2022.2160317"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.clpt.6100406"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.12692"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2215-0366(19)30088-4"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40291-013-0028-5"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00210-003-0832-2"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/138920010791196274"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.2217\/pgs.14.155"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.15651"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1124\/dmd.122.000957"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00228-023-03462-y"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40246-024-00579-8"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3380"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.3106"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/cts.13743"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.15721"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/bcp.70004"},{"key":"e_1_2_9_28_1","unstructured":"Ministry of Agriculture Forestry and Fisheries Japan Food Balance Sheet. (in Japanese)accessed at 5 January 2026 https:\/\/www.maff.go.jp\/j\/tokei\/kouhyou\/zyukyu\/index.html."},{"key":"e_1_2_9_29_1","unstructured":"Food and Agriculture Organization of the United Nations Food Balances (2010\u2013)accessed at 5 January 2026 https:\/\/www.fao.org\/faostat\/en\/#data\/FBS."},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/cpt.1768"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2012.05.110"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.c20-00336"},{"key":"e_1_2_9_33_1","unstructured":"Food and Drug Administration Bioanalytical Method Validation Guidance for Industryaccessed at 16 September 2025 https:\/\/www.fda.gov\/media\/70858\/download."},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b20-00400"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M093971"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b22-00840"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.1241"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dmpk.2019.07.003"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.2133\/dmpk.20.294"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1996.00489.x"},{"key":"e_1_2_9_41_1","unstructured":"Pharmacogene Variation Consortium CYP2D6accessed at 16 September 2025 https:\/\/www.pharmvar.org\/gene\/CYP2D6."},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1208\/aapsj0901011"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11095-007-9291-7"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-007-0082-2"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.2000.00209.x"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b19-00512"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41397-022-00288-2"},{"key":"e_1_2_9_48_1","unstructured":"Pharmaceuticals and Medical Devices Agency Strattera Capsuleaccessed at 8 January 2026 https:\/\/www.pmda.go.jp\/PmdaSearch\/iyakuDetail\/ResultDataSetPDF\/530471_1179050M1023_1_21."},{"key":"e_1_2_9_49_1","unstructured":"Pharmaceuticals and Medical Devices Agency Dysval CapsulesAccessed at 8 January 2026 https:\/\/pins.japic.or.jp\/pdf\/newPINS\/00071650.pdf."},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2007.07.009"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.2217\/fon.13.168"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1177\/096032718500400209"}],"container-title":["Clinical and Translational Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70668","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cts.70668","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cts.70668","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T13:38:05Z","timestamp":1787405885000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascpt.onlinelibrary.wiley.com\/doi\/10.1111\/cts.70668"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":51,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8]]}},"alternative-id":["10.1111\/cts.70668"],"URL":"https:\/\/doi.org\/10.1111\/cts.70668","archive":["Portico"],"relation":{},"ISSN":["1752-8054","1752-8062"],"issn-type":[{"value":"1752-8054","type":"print"},{"value":"1752-8062","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]},"assertion":[{"value":"2026-01-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-26","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-20","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70668"}}