{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T18:31:59Z","timestamp":1789583519573,"version":"build-2803163510"},"reference-count":25,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T00:00:00Z","timestamp":1782259200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"QuadMedicine"},{"name":"Ministry of Health & Welfare, Republic of Korea","award":["RS-2024-00408877"],"award-info":[{"award-number":["RS-2024-00408877"]}]},{"DOI":"10.13039\/501100002642","name":"Korea University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002642","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: Semaglutide, a long-acting glucagon-like peptide-1 (GLP-1) analog for type 2 diabetes and obesity, requires sensitive and high-throughput bioanalytical methods to support pharmacokinetic studies. However, previously reported liquid chromatography\u2013tandem mass spectrometry (LC\u2013MS\/MS) assays have been limited by lengthy run times (~18 min) and suboptimal sensitivity. This study aimed to develop and validate a rapid, sensitive LC\u2013MS\/MS method for quantifying semaglutide in plasma. Methods: Plasma samples (50 \u03bcL) were prepared by acetone-mediated protein precipitation followed by solid-phase extraction. Chromatographic separation was performed on a Cadenza CD-C18 MF column within 9 min, using positive electrospray ionization in multiple reaction monitoring mode with the transitions m\/z 1029.4 \u2192 110.1 for semaglutide and m\/z 938.9 \u2192 109.9 for liraglutide (internal standard). Validation followed the U.S. Food and Drug Administration (FDA) bioanalytical guidelines. Results: The assay showed a lower limit of quantification of 1 ng\/mL with linearity across 1\u2013500 ng\/mL (R2 = 0.9999), with sharp peak shape and no carryover. Intra- and inter-day accuracies were 95.69\u2013103.76% and 94.93\u2013100.08%, with precision \u22644.50% and \u22645.88%. Recovery (93.05\u2013107.95%) and matrix effects (96.34\u2013104.12%) were consistent across quality control levels, and the analyte was stable under all tested conditions. The method was successfully applied to a pharmacokinetic study in Sprague\u2013Dawley rats following subcutaneous administration of 50 \u03bcg semaglutide. Conclusions: The validated method offers shorter analysis time, improved sensitivity, and reduced sample volume compared with previously reported assays, supporting its application in preclinical pharmacokinetic studies of semaglutide and related GLP-1 analogs.<\/jats:p>","DOI":"10.3390\/pharmaceutics18070770","type":"journal-article","created":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:52:11Z","timestamp":1782453131000},"page":"770","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Development and Validation of a Liquid Chromatography\/Tandem Mass Spectrometry Method for the Quantification of the GLP-1 Analog Semaglutide in Rat Plasma, and Its Application in a Pharmacokinetic Study"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2173-9288","authenticated-orcid":false,"given":"Jong-Min","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Clinical Pharmacology and Toxicology, Anam Hospital, Korea University College of Medicine, Seoul 02841, Republic of Korea"},{"name":"Institute of Medical Information and Data Convergence, Korea University College of Medicine, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyoung-Ah","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Toxicology, Anam Hospital, Korea University College of Medicine, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na-Young","family":"Yu","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0093-3874","authenticated-orcid":false,"given":"Dae-Duk","family":"Kim","sequence":"additional","affiliation":[{"name":"College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul 08826, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Yeon","family":"Kang","sequence":"additional","affiliation":[{"name":"QuadMedicine R&D Centre, QuadMedicine Inc., Seongnam 13209, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung-Ki","family":"Baek","sequence":"additional","affiliation":[{"name":"QuadMedicine R&D Centre, QuadMedicine Inc., Seongnam 13209, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5548-3378","authenticated-orcid":false,"given":"Jin-Woo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Toxicology, Anam Hospital, Korea University College of Medicine, Seoul 02841, Republic of Korea"},{"name":"Department of Neurology, Anam Hospital, Korea University College of Medicine, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji-Young","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Toxicology, Anam Hospital, Korea University College of Medicine, Seoul 02841, Republic of Korea"},{"name":"Institute of Medical Information and Data Convergence, Korea University College of Medicine, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,24]]},"reference":[{"key":"ref_1","unstructured":"Novo Nordisk (2026, February 01). 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