{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T02:33:44Z","timestamp":1784687624945,"version":"3.55.0"},"reference-count":27,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFF0600701"],"award-info":[{"award-number":["2021YFF0600701"]}],"id":[{"id":"10.13039\/501100012166","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":[[2026,4,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Linaclotide is an important peptide drug used to treat irritable bowel syndrome with constipation (IBS\u2010C). However, structurally related impurities in peptide drugs can be generated during synthesis, storage, or transport, which compromise the quality and safety. Therefore, developing a highly sensitive analytical method for impurity detection is of great significance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A liquid chromatography\u2013high resolution mass spectrometry (LC\u2010HRMS) method was developed. Linaclotide samples were directly analyzed using an Orbitrap mass spectrometer with an electrospray ionization (ESI) source operated in positive ion mode. Tandem mass spectrometry with collision\u2010induced dissociation was utilized. The method leveraged high mass accuracy to identify and quantify structurally related peptide impurities in linaclotide samples from different manufacturers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The method was applied to characterize the peptide impurities in linaclotide study materials. In manufacturer A's material, [Des\u2010Tyr\n                      <jats:sup>14<\/jats:sup>\n                      ]\u2010linaclotide was found at 0.453\u2009mg\/g. The same impurity was found in manufacturer B's material at 0.768\u2009mg\/g, as well as another impurity [endo\u2010Ala\n                      <jats:sup>9<\/jats:sup>\n                      ]\u2010linaclotide at 0.555\u2009mg\/g.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The developed LC\u2010HRMS method successfully addresses the challenge of determining structurally related peptide impurities in linaclotide. Its ability to characterize specific impurities provides a valuable complement to existing quality control strategies for peptide therapeutics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.70030","type":"journal-article","created":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T03:36:11Z","timestamp":1768534571000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Identification and Quantification of Structurally Related Peptide Impurity in Linaclotide by Liquid Chromatography\u2013High Resolution Mass Spectrometry"],"prefix":"10.1002","volume":"40","author":[{"given":"Jinlan","family":"Cheng","sequence":"first","affiliation":[{"name":"School of Pharmacy China Medical University  Shenyang China"},{"name":"National Institute of Metrology Division of Chemical Metrology &amp; Analytical Science  Beijing P. R. 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