{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T16:50:37Z","timestamp":1787676637941,"version":"build-2784847793"},"reference-count":20,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,1,12]],"date-time":"2026-01-12T00:00:00Z","timestamp":1768176000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100002858","name":"China Postdoctoral Science Foundation","doi-asserted-by":"publisher","award":["2024M762166"],"award-info":[{"award-number":["2024M762166"]}],"id":[{"id":"10.13039\/501100002858","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biomedical Chromatography"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Pharmaceutical excipients have traditionally been regarded as pharmacologically inert carriers, serving merely as vehicles for active pharmaceutical ingredients. However, this conventional paradigm is increasingly challenged by emerging evidence revealing clinically significant drug\u2013excipient interactions that can profoundly influence therapeutic outcomes. This study investigates a previously unrecognized pharmacokinetic interaction between nimodipine, a dihydropyridine calcium channel blocker, and polysorbate 80, a commonly used solubilizing excipient in nimodipine formulations. A novel HPLC\u2013MS\/MS method for simultaneous quantification of nimodipine and polysorbate 80 was developed and validated, achieving excellent analytical performance with linearity (\n                    <jats:italic>r<\/jats:italic>\n                    \u2009&gt;\u20090.995), precision (RSD\u2009&lt;\u200915%), and accuracy (RE\u2009&lt;\u200915%). Pharmacokinetic studies in rats revealed that polysorbate 80 co\u2010administration dramatically enhanced nimodipine systemic exposure, increasing AUC by 51.1%, decreasing clearance by 36.5%, and prolonging half\u2010life by 16.1%. Mechanistic investigations using rat liver microsomes demonstrated that polysorbate 80 competitively inhibited nimodipine metabolism with an IC\n                    <jats:sub>50<\/jats:sub>\n                    of 103.30\u2009\u03bcmol\/L and\n                    <jats:italic>K<\/jats:italic>\n                    <jats:sub>i<\/jats:sub>\n                    of 94.35\u2009\u03bcmol\/L, while remaining minimally metabolized itself. These findings provide the first evidence of a clinically significant pharmacokinetic interaction between nimodipine and polysorbate 80, challenging the assumption of excipient inertness and highlighting the critical importance of evaluating excipient\u2013drug interactions in pharmaceutical development and clinical practice.\n                  <\/jats:p>","DOI":"10.1002\/bmc.70330","type":"journal-article","created":{"date-parts":[[2026,1,13]],"date-time":"2026-01-13T08:34:34Z","timestamp":1768293274000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Hidden Drug\u2010Excipient Interaction by HPLC\u2013MS\/MS Analysis: Polysorbate 80 Enhances Nimodipine Systemic Exposure Through Competitive Metabolic Inhibition"],"prefix":"10.1002","volume":"40","author":[{"given":"Jiameng","family":"Qu","sequence":"first","affiliation":[{"name":"School of Pharmacy Shenyang Pharmaceutical University  Shenyang 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Pharmaceutical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongsheng","family":"Zong","sequence":"additional","affiliation":[{"name":"School of Medical Devices Shenyang Pharmaceutical University  Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3087-4692","authenticated-orcid":false,"given":"Qing","family":"Li","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shenyang Pharmaceutical University  Shenyang 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