{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T11:11:16Z","timestamp":1788779476911,"version":"build-2803163510"},"reference-count":21,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22336004"],"award-info":[{"award-number":["22336004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22522610"],"award-info":[{"award-number":["22522610"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["22476172"],"award-info":[{"award-number":["22476172"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2026,10,30]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>The comprehensive quality control of chiral pharmaceuticals like mitiglinide necessitates simultaneous assessment of chemical impurities and enantiomeric purity, yet conventional workflows address these separately, leading to inefficiency. This study develops a comprehensive analytical strategy to overcome this challenge for the anti\u2010diabetic drug mitiglinide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>For chiral analysis, an online heart\u2010cutting two\u2010dimensional liquid chromatography\u2013high\u2010resolution mass spectrometry (2D\u2010LC\u2010HRMS) method was developed. First, impurity profiling of mitiglinide was accomplished using a one\u2010dimensional reversed\u2010phase LC\u2010HRMS (1D\u2010LC\u2010HRMS) method. Subsequently, the 2D\u2010LC\u2010HRMS system achieved enantiomer separation by online coupling of a C18 column (first dimension) with a polysaccharide\u2010based chiral column (second dimension), with the separated analytes detected by an Orbitrap mass spectrometer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>1D\u2010LC\u2010HRMS identified five major impurities, structurally characterizing four, with the main component accounting for only 49.12% of the total integrated peak area (relative abundance by EIC peak area normalization, not absolute purity). The 2D\u2010LC\u2010HRMS method achieved effective enantiomer separation. A consistent third minor chromatographic peak was observed across six replicate analyses, which is tentatively assigned as a potential diastereomeric impurity based on stereochemical interpretation of the chromatographic behavior; confirmatory evidence is required for definitive identification.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This work successfully establishes a comprehensive strategy that efficiently consolidates impurity profiling and chiral purity assessment for mitiglinide. It provides a reliable, more informative approach for the quality control of complex chiral pharmaceuticals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.70144","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T09:46:13Z","timestamp":1785577573000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrated 1D\u2010LC\u2010HRMS and Heart\u2010Cutting 2D\u2010LC\u2013MS for Impurity Profiling and Chiral Separation of Mitiglinide Drug Substance"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-5862-4525","authenticated-orcid":false,"given":"Chenxi","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Chemistry Zhejiang University  Zhejiang Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiwen","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Chemistry Zhejiang University  Zhejiang Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1555-0391","authenticated-orcid":false,"given":"Wanhao","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Chemistry Zhejiang University  Zhejiang Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2900-2600","authenticated-orcid":false,"given":"Yuanjiang","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Chemistry Zhejiang University  Zhejiang Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1021-6775","authenticated-orcid":false,"given":"Hongru","family":"Feng","sequence":"additional","affiliation":[{"name":"Department of Chemistry Zhejiang University  Zhejiang Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,1]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1517\/14656566.9.15.2691"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.59566\/IJBS.2006.2085"},{"key":"e_1_2_8_4_1","volume-title":"Impurities in New Drug Substances Q3A(R2) [Guideline]","author":"ICH Harmonised Tripartite Guideline","year":"2006"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1248\/cpb.46.337"},{"key":"e_1_2_8_6_1","unstructured":"J. P.LecouveandJ. C.Fugier. \u201cMethod for Preparing a Substituted Perhydroisoindole \u201d WO 9901430 1999. Patent."},{"issue":"4","key":"e_1_2_8_7_1","first-page":"412","article-title":"Reversed\u2010Phase Liquidchromatography Separation and Mass Spectrometry Fragmentation Analysis of Mitiglinide and Three Isomers","volume":"37","author":"Li M.","year":"2019","journal-title":"Se Pu"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2022.115205"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2022.463215"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2021.114466"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jssc.201400734"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2023.464565"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcoa.2024.100132"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.6b03506"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2024.464824"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/D4AY01723A"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1039\/D5AY00234A"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.5c02658"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chroma.2019.03.028"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/ijch.201100151"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules29061346"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcoa.2024.100122"}],"container-title":["Rapid Communications in Mass Spectrometry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rcm.70144","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/rcm.70144","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/rcm.70144","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T10:40:40Z","timestamp":1788777640000},"score":1,"resource":{"primary":{"URL":"https:\/\/analyticalsciencejournals.onlinelibrary.wiley.com\/doi\/10.1002\/rcm.70144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,1]]},"references-count":21,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2026,10,30]]}},"alternative-id":["10.1002\/rcm.70144"],"URL":"https:\/\/doi.org\/10.1002\/rcm.70144","archive":["Portico"],"relation":{},"ISSN":["0951-4198","1097-0231"],"issn-type":[{"value":"0951-4198","type":"print"},{"value":"1097-0231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,1]]},"assertion":[{"value":"2026-03-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-13","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-01","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70144"}}