{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:06:28Z","timestamp":1791378388452,"version":"4.3.2"},"reference-count":22,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"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":["J of Separation Science"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Dalbavancin hydrochloride (DB) is a semi\u2011synthetic lipoglycopeptide antibiotic whose pharmacopeial impurity analysis relies on mobile phases containing non\u2011volatile phosphate buffers. Although effective for separation, these buffers are incompatible with mass spectrometry (MS), impeding structural characterization of trace impurities. In this study, a heart\u2011cutting two\u2011dimensional liquid chromatography\/high\u2011resolution MS (2D\u2011LC\/HRMS) method was developed to overcome this limitation. The first dimension employed a dual\u2011column serial system with a phosphate\u2011based mobile phase to achieve high\u2011resolution separation of dalbavancin and its related substances. Target fractions were online transferred to a second dimension with MS\u2011compatible conditions for desalting and accurate mass analysis. Using this approach, 22 components\u2014including five major components (DB\u2011A0, DB\u2011A1, DB\u2011B0, DB\u2011B1, and DB\u2011B2) and 17 impurities (e.g., DB\u2011R1, DB\u2011R2, DB\u2011D0, DB\u2011D1, DB\u2011C0, DB\u2011C1, RRT0.94, and RRT0.96)\u2014were identified based on accurate mass and tandem MS fragmentation patterns, with confirmation by reference standards where available. To support routine quality control, three complementary high\u2010performance LC methods were developed and fully validated according to ICH guidelines for the quantification of related substances, specific impurities DBa\/RRT1.12\/RRT1.15, and the highly polar impurity DB\u2011R6. Forced\u2011degradation studies under thermal, photolytic, acidic, alkaline, and oxidative conditions revealed distinct degradation behaviors: DB\u2011R1 increased markedly under thermal, acidic, and photolytic stress; DB\u2011R2 was the primary alkaline degradation product; DBa and RRT0.96 increased markedly under oxidative conditions; and DB\u2011R6 increased markedly under acidic conditions. This integrated analytical workflow provides a robust platform for both impurity characterization and routine quality control of DB, supporting process optimization and stability assessment.<\/jats:p>","DOI":"10.1002\/jssc.70545","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T12:46:07Z","timestamp":1791377167000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heart\u2011Cutting Two\u2011Dimensional Liquid Chromatography\/High\u2011Resolution Mass Spectrometry and Complementary High\u2010Performance Liquid Chromatography Methods for Comprehensive Impurity Profiling and Quality Control of Dalbavancin Hydrochloride"],"prefix":"10.1002","volume":"49","author":[{"given":"Hongling","family":"Xu","sequence":"first","affiliation":[{"name":"College of Pharmaceutical Science Soochow University  Suzhou P. R. China"},{"name":"BrightGene Bio\u2010Medical Technology Co., Ltd  Suzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-3044-9836","authenticated-orcid":false,"given":"Xinying","family":"Du","sequence":"additional","affiliation":[{"name":"College of Pharmaceutical Science Soochow University  Suzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinjin","family":"Lv","sequence":"additional","affiliation":[{"name":"BrightGene Bio\u2010Medical Technology Co., Ltd  Suzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Liu","sequence":"additional","affiliation":[{"name":"BrightGene Bio\u2010Medical Technology Co., Ltd  Suzhou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xincheng","family":"Shen","sequence":"additional","affiliation":[{"name":"BrightGene Bio\u2010Medical Technology Co., Ltd  Suzhou P. R. 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