{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T01:49:12Z","timestamp":1785894552300,"version":"3.56.0"},"reference-count":48,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T00:00:00Z","timestamp":1728864000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Plan for Science, Technology, and Innovation (MAARIFAH), King Abdulaziz City for Science and Technology, Saudi Arabia","award":["14-MED-543-02"],"award-info":[{"award-number":["14-MED-543-02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Proteomes"],"abstract":"<jats:p>Current immunoassay techniques for analyzing clinically relevant parathyroid hormone (PTH) circulating fragments cannot distinguish microheterogeneity among structurally similar molecular species. This hinders the identification of molecular species and the capture of target analyte information. Since structural modifications are important in disease pathways, mass spectrometry can detect, identify, and quantify heterogeneous ligands captured by antibodies. We aimed to create a sensitive and selective multiple reaction monitoring\u2013mass spectrometric immunoassay analysis (MRM-MSIA)-based method for detecting and quantifying PTH fragments or proteoforms for clinical research. Our study established MRM transitions using triple-quadrupole tandem mass spectrometry for the signature peptides of five PTH fragments. This method was validated according to FDA guidelines, employing the mass spectrometric immunoassay (MSIA) protocol to bolster detection selectivity and sensitivity. This validated approach was applied by analyzing samples from type 2 diabetes mellitus (T2DM) patients with and without vitamin D deficiency. We found serum PTH fragments associated with vitamin D deficiency in patients with and without T2DM. We developed and validated the MRM-MSIA technique specifically designed for the detection and quantification (amino acid (aa38\u201344), (aa45\u201351), and (aa65\u201375)) of these fragments associated with vitamin D deficiency and T2DM. This study is the first to accurately quantify plasma PTH fragments using MRM-MSIA, demonstrating its potential for clinical diagnostics.<\/jats:p>","DOI":"10.3390\/proteomes12040030","type":"journal-article","created":{"date-parts":[[2024,10,14]],"date-time":"2024-10-14T12:44:31Z","timestamp":1728909871000},"page":"30","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Multiple Reaction Monitoring\u2013Mass Spectrometric Immunoassay Analysis of Parathyroid Hormone Fragments with Vitamin D Deficiency in Patients with Diabetes Mellitus"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9745-2959","authenticated-orcid":false,"given":"Hicham","family":"Benabdelkamel","sequence":"first","affiliation":[{"name":"Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0545-3311","authenticated-orcid":false,"given":"Refat M.","family":"Nimer","sequence":"additional","affiliation":[{"name":"Department of Medical Laboratory Sciences, Jordan University of Science and Technology, Irbid 22110, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8082-9326","authenticated-orcid":false,"given":"Afshan","family":"Masood","sequence":"additional","affiliation":[{"name":"Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2244-6842","authenticated-orcid":false,"given":"Maha","family":"Al Mogren","sequence":"additional","affiliation":[{"name":"Metabolomics Section, Department of Clinical Genomics, Center for Genome Medicine, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9527-9424","authenticated-orcid":false,"given":"Anas M.","family":"Abdel Rahman","sequence":"additional","affiliation":[{"name":"Metabolomics Section, Department of Clinical Genomics, Center for Genome Medicine, King Faisal Specialist Hospital and Research Centre (KFSHRC), Riyadh 11211, Saudi Arabia"},{"name":"Department of Biochemistry and Molecular Medicine, College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4792-5188","authenticated-orcid":false,"given":"Assim A.","family":"Alfadda","sequence":"additional","affiliation":[{"name":"Proteomics Resource Unit, Obesity Research Center, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia"},{"name":"Department of Medicine, College of Medicine, King Saud University, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1053\/meta.2000.17708","article-title":"Insulin sensitivity is inversely correlated with plasma intact parathyroid hormone level","volume":"49","author":"Chiu","year":"2000","journal-title":"Metabolism"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1093\/ajcn\/79.5.820","article-title":"Hypovitaminosis D is associated with insulin resistance and beta cell dysfunction","volume":"79","author":"Chiu","year":"2004","journal-title":"Am. 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