{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T20:24:19Z","timestamp":1790195059383,"version":"4.1.0"},"reference-count":119,"publisher":"Wiley","license":[{"start":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T00:00:00Z","timestamp":1764720000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Mass Spectrometry Reviews"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Matrix\u2010assisted laser desorption\/ionization mass spectrometry imaging (MALDI\u2010MSI) has rapidly advanced in biomedical research, enabling label\u2010free, untargeted spatial detection of metabolites, lipids, proteins, and glycans in tissue sections. However, challenges such as low ionization efficiency and chemical instability limit the detection of certain molecules. To address these issues, on\u2010tissue chemical derivatization (OTCD) has been widely applied as an effective strategy to enhance imaging capabilities. This review systematically summarizes the development of derivatization reagents targeting different reactive functional groups and their applications in MALDI\u2010MSI, including strategies for the derivatization of amines, carbonyls, carboxyls, double bonds, hydroxyls, thiols, and platinum\u2010based drugs. Particular attention is given to how these derivatization reagents enhance the detection range and biological relevance by increasing molecular weight, improving ionization efficiency, and reducing background noise interference. Additionally, we explore the application of OTCD in various biological samples and discuss challenges related to experimental workflows, derivatization efficiency, and tissue integrity. This review provides important theoretical support for the advancement of MSI technology and highlights its broad potential applications in biomedical research.<\/jats:p>","DOI":"10.1002\/mas.70016","type":"journal-article","created":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T05:34:23Z","timestamp":1764826463000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Recent Advances in On\u2010Tissue Chemical Derivatization Strategies for Enhancing MALDI\u2010MSI"],"prefix":"10.1002","author":[{"given":"Meng","family":"Huang","sequence":"first","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine Shanghai China"},{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyu","family":"Qi","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China"},{"name":"School of Pharmacy Shenyang Pharmaceutical University Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8301-7999","authenticated-orcid":false,"given":"Dafu","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhou","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Yuan","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Danijela","family":"Mi\u0161i\u0107","sequence":"additional","affiliation":[{"name":"China\u2010Serbia \u201cBelt and Road\u201d Joint Laboratory for Natural Products and Drug Discovery Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Sokovi\u0107","sequence":"additional","affiliation":[{"name":"China\u2010Serbia \u201cBelt and Road\u201d Joint Laboratory for Natural Products and Drug Discovery Institute for Biological Research \u201cSini\u0161a Stankovi\u0107\u201d Belgrade Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongxi","family":"Xu","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Sun","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shenyang Pharmaceutical University Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Ye","sequence":"additional","affiliation":[{"name":"School of Pharmacy Shanghai University of Traditional Chinese Medicine Shanghai China"},{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China"},{"name":"China\u2010Serbia \u201cBelt and Road\u201d Joint Laboratory for Natural Products and Drug Discovery Shanghai Institute of Materia Medica, Chinese Academy of Sciences Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8167-9750","authenticated-orcid":false,"given":"Jia","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Institute of Materia Medica Chinese Academy of Sciences Shanghai China"},{"name":"School of Pharmacy Shenyang Pharmaceutical University Shenyang China"},{"name":"School of Pharmaceutical Science and Technology, Hangzhou Institute for Advanced Study University of Chinese Academy of Sciences Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,3]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"crossref","first-page":"5704","DOI":"10.1039\/D4AN01260G","article-title":"Exploring Gunshot Residue Detection in Fingerprints by Functionalized Particle\u2010Coupled Matrix\u2010Assisted Laser Desorption\/Ionization Mass Spectrometry","volume":"149","author":"Adav S. 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