{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,30]],"date-time":"2025-08-30T05:40:04Z","timestamp":1756532404668,"version":"3.44.0"},"reference-count":40,"publisher":"Walter de Gruyter GmbH","issue":"10","license":[{"start":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T00:00:00Z","timestamp":1747872000000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,9,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec id=\"j_cclm-2025-0189_abs_001\">\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>Histamine, mainly produced in mast cells (MC), plays a key role in allergy and inflammation. Measuring its urinary metabolites, N-methylhistamine (NMH) and 1-methyl-4-imidazoleacetic acid (MIMA), is essential in assessing histamine-related pathologies. Patients with concurrent systemic mastocytosis (SM) and hereditary alpha tryptasemia (H\u03b1T) may show increased MC mediator-related symptom severity. We developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS\/MS) assay to quantify histamine, NMH, and MIMA, and explored their correlation with basal serum tryptase (BST) levels.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2025-0189_abs_002\">\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Using an in-matrix double derivatization, enhancing extraction, we analyzed urinary histamine, NMH, and MIMA with an online solid-phase extraction LC-MS\/MS system. Analytical method validation assessed recovery, imprecision, and detection limits. For clinical validation, correlation analysis between BST levels, NMH, and MIMA in SM and H\u03b1T patients was performed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2025-0189_abs_003\">\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The assay demonstrated recoveries&gt;98\u202f%, imprecision&lt;3\u202f%, and limits of quantification at 2.0\u202fnmol\/L for histamine, 0.53\u202fnmol\/L for NMH, and 0.011\u202f\u03bcmol\/L for MIMA. Patients with a combination of SM and H\u03b1T showed a 2.6\u20133.6 fold increase in BST compared to those with SM alone. A BST\/NMH ratio&gt;0.129 predicted H\u03b1T with 91.3\u202f% sensitivity and 85.6\u202f% specificity, and a BST\/MIMA ratio&gt;7.46 predicted H\u03b1T with 89.9\u202f% sensitivity and 86.0\u202f% specificity, independent of SM status.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec id=\"j_cclm-2025-0189_abs_004\">\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our LC-MS\/MS method provides highly accurate and efficient quantification of histamine, NMH, and MIMA. Integrating BST\/NMH and BST\/MIMA ratios in diagnostic protocols enhances detection of H\u03b1T in MC-related disorders, supporting improved diagnostics and tailored patient management.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1515\/cclm-2025-0189","type":"journal-article","created":{"date-parts":[[2025,5,22]],"date-time":"2025-05-22T15:15:11Z","timestamp":1747926911000},"page":"2002-2011","source":"Crossref","is-referenced-by-count":0,"title":["Histamine metabolite to basal serum tryptase ratios in systemic mastocytosis and hereditary alpha tryptasemia using a validated LC-MS\/MS approach"],"prefix":"10.1515","volume":"63","author":[{"given":"Abdulrazzaq","family":"Alheraky","sequence":"first","affiliation":[{"name":"Department of Laboratory Medicine , 10173 University Medical Center Groningen, University of Groningen , Groningen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claude P.","family":"Van Der Ley","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine , 10173 University Medical Center Groningen, University of Groningen , Groningen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martijn","family":"Van Faassen","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine , 10173 University Medical Center Groningen, University of Groningen , Groningen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Saskia K.","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Hematology , University Medical Center Groningen, University of Groningen , Groningen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanneke N.G.","family":"Oude Elberink","sequence":"additional","affiliation":[{"name":"Department of Allergology , Groningen , The Netherlands"},{"name":"Groningen Research Institute for Asthma and COPD (GRIAC) , University Medical Center Groningen, University of Groningen , Groningen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caroline","family":"Roozendaal","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine , 10173 University Medical Center Groningen, University of Groningen , Groningen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michel J.","family":"Vos","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine , 10173 University Medical Center Groningen, University of Groningen , Groningen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andr\u00e9 B.","family":"Mulder","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine , 10173 University Medical Center Groningen, University of Groningen , Groningen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ido P.","family":"Kema","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine , 10173 University Medical Center Groningen, University of Groningen , Groningen , The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"374","published-online":{"date-parts":[[2025,5,22]]},"reference":[{"key":"2025083005004159108_j_cclm-2025-0189_ref_001","doi-asserted-by":"crossref","unstructured":"Thangam, EB, Jemima, EA, Singh, H, Baig, MS, Khan, M, Mathias, CB, et al.. 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