{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T15:12:33Z","timestamp":1780585953605,"version":"3.54.1"},"reference-count":12,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2026,7,30]]},"abstract":"ABSTRACT<\/jats:title>\n \n Rationale<\/jats:title>\n Impurity profiling is critical for the quality control and safety assessment of pharmaceutical formulations. Tolterodine tartrate tablets contain unknown impurities that are not documented in standard literature or pharmacopoeias. Identifying these impurities and determining their origin is essential for optimizing the manufacturing process and ensuring product stability.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n A comprehensive two\u2010dimensional liquid chromatography\u2010mass spectrometry (2D\u2010LC\/MS) method was developed. The first\u2010dimension separation used a Waters XBridge C18 column (4.6\u2009\u00d7\u2009250\u2009mm, 5\u2009\u03bcm) with gradient elution (mobile phase A: acetonitrile\/water\/perchloric acid, 200:800:1.5, v\/v\/v; mobile phase B: acetonitrile) at 65\u00b0C and 1.0\u2009mL\u00b7min\n \u22121<\/jats:sup>\n . The second\u2010dimension analysis employed an Agilent Poroshell 120 EC\u2010C18 column (2.1\u2009\u00d7\u2009100\u2009mm, 2.7\u2009\u03bcm) under isocratic conditions (acetonitrile\/20\u2009mmol\u00b7L\n \u22121<\/jats:sup>\n ammonium formate, pH\u20093.0, 45:55) at 30\u00b0C and 0.3\u2009mL\u00b7min\n \u22121<\/jats:sup>\n . Detection was performed using an Agilent 6538 Q\u2010TOF mass spectrometer with ESI in positive ion mode (capillary voltage: 4000\u2009V; nebulizer pressure: 35\u2009psi; drying gas: 10\u2009L\u00b7min\n \u22121<\/jats:sup>\n at 350\u00b0C; scan range:\n m\/z<\/jats:italic>\n 50\u20131000). Impurity structures were elucidated by comparing their fragmentation patterns with tolterodine and considering the synthesis pathway. A comparative stability study of the API and tablets under stress conditions was conducted to trace impurity origins.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n Three primary impurities were detected and characterized in tablets from three different manufacturers, including the originator product. One previously unreported impurity (Impurity 1) was identified. Stability studies indicated that this impurity is a degradation product generated specifically during the tablet formulation process, not from the drug substance itself.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The established 2D\u2010LC\/MS method is effective for the structural elucidation and source tracking of impurities in tolterodine tartrate tablets. The identification of a process\u2010related degradation product provides direct insights for enhancing formulation strategies and implementing targeted quality control measures.<\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/rcm.70084","type":"journal-article","created":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T10:51:02Z","timestamp":1776768662000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Analysis of Major Impurities in Tolterodine Tartrate Tablets by 2D\u2010UPLC\u2010Q\u2010TOF\/MS"],"prefix":"10.1002","volume":"40","author":[{"given":"Fangfang","family":"Pan","sequence":"first","affiliation":[{"name":"Zhejiang Institute for Food and Drug Control, National Medical Products Administration Key Laboratory for Core Technology of Generic Drug Evaluation, Zhejiang Key Laboratory of Biopharmaceutical Contact Materials Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6680-5413","authenticated-orcid":false,"given":"Zhuyu","family":"Jin","sequence":"additional","affiliation":[{"name":"Zhejiang Institute for Food and Drug Control, National Medical Products Administration Key Laboratory for Core Technology of Generic Drug Evaluation, Zhejiang Key Laboratory of Biopharmaceutical Contact Materials Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghai","family":"Xu","sequence":"additional","affiliation":[{"name":"Zhejiang Institute for Food and Drug Control, National Medical Products Administration Key Laboratory for Core Technology of Generic Drug Evaluation, Zhejiang Key Laboratory of Biopharmaceutical Contact Materials Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianan","family":"Wang","sequence":"additional","affiliation":[{"name":"Zhejiang Institute for Food and Drug Control, National Medical Products Administration Key Laboratory for Core Technology of Generic Drug Evaluation, Zhejiang Key Laboratory of Biopharmaceutical Contact Materials Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Gu","sequence":"additional","affiliation":[{"name":"Zhejiang Institute for Food and Drug Control, National Medical Products Administration Key Laboratory for Core Technology of Generic Drug Evaluation, Zhejiang Key Laboratory of Biopharmaceutical Contact Materials Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Shao","sequence":"additional","affiliation":[{"name":"Zhejiang Institute for Food and Drug Control, National Medical Products Administration Key Laboratory for Core Technology of Generic Drug Evaluation, Zhejiang Key Laboratory of Biopharmaceutical Contact Materials Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0024\u20103205(97)00057\u2010X"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1515\/acph\u20102017\u20100027"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0016718"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002512\u2010200118040\u201000005"},{"key":"e_1_2_9_6_1","first-page":"339","volume-title":"Profiles of Drug Substances, Excipients and Related Methodology","author":"Ananchenko G.","year":"2017"},{"key":"e_1_2_9_7_1","unstructured":"Z. Y.Xu \u201cA Tolterodine Tartrate Tablet. CN Patent 105832685A \u201d (2016)."},{"key":"e_1_2_9_8_1","unstructured":"The United States Pharmacopeial Convention \u201cU.S. Pharmacopeia\u2010National Formulary \u201d (2025)."},{"key":"e_1_2_9_9_1","volume-title":"European Pharmacopoeia","author":"European Directorate for the Quality of Medicines and Healthcare","year":"2025"},{"key":"e_1_2_9_10_1","unstructured":"National Standard of National Medical Products Administration \u201cWS1\u2010(X\u2010182)\u20102003Z.\u201d"},{"issue":"21","key":"e_1_2_9_11_1","first-page":"2561","article-title":"LC\u2010MS Identification of Related Substances in Tolterodine Tartrate","volume":"22","author":"Yu L.","year":"2013","journal-title":"Chinese Journal of New Drugs"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3797\/scipharm.1407\u201018"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/mas.21845"}],"container-title":["Rapid Communications in Mass Spectrometry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rcm.70084","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/rcm.70084","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rcm.70084","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:52:06Z","timestamp":1780584726000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/rcm.70084"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,21]]},"references-count":12,"journal-issue":{"issue":"14","published-print":{"date-parts":[[2026,7,30]]}},"alternative-id":["10.1002\/rcm.70084"],"URL":"https:\/\/doi.org\/10.1002\/rcm.70084","archive":["Portico"],"relation":{},"ISSN":["0951-4198","1097-0231"],"issn-type":[{"value":"0951-4198","type":"print"},{"value":"1097-0231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,4,21]]},"assertion":[{"value":"2026-01-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-03-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-21","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70084"}}