{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:18:28Z","timestamp":1790381908552,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:00:00Z","timestamp":1760313600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Diamorphine (DIM, heroin) is a semi-synthetic opioid that undergoes rapid conversion to 6-monoacetylmorphine and morphine, producing short-lived biomarkers that are difficult to capture during the process. This review critically explores the evolution of analytical techniques for quantitative DIM analysis in biological matrices from 1980 to 2025. It synthesizes findings across blood, plasma, urine, hair, sweat, and postmortem samples, emphasizing matrix-specific challenges and forensic applicability. Unlike previous opioid reviews that primarily focused on metabolites, this work highlights analytical methods capable of successfully detecting diamorphine itself alongside its key metabolites. This review examines 32 studies spanning three decades and compares three core analytical methods: gas chromatography\u2013mass spectrometry (GC\u2013MS), high-performance liquid chromatography (HPLC) with optical detection and liquid chromatography\u2013mass spectrometry (LC\u2013MS). Key performance metrics include sensitivity, sample preparation workflow, hydrolysis control, metabolite coverage, matrix compatibility, automation potential and throughput. GC\u2013MS remains the workhorse for hair and sweat ultra-trace screening after derivatization. HPLC with UV, fluorescence or diode-array detection enables robust quantification of morphine and its glucuronides in pharmacokinetic and clinical settings. LC\u2013MS facilitates the multiplexed analysis of DIM, its ester metabolites and its conjugates in a single, rapid run under gentle conditions to prevent ex vivo degradation. Recent advances such as high-resolution mass spectrometry and microsampling techniques offer new opportunities for sensitive and matrix-adapted analysis. By integrating validation parameters, forensic applicability, and evolving instrumentation, this review provides a practical roadmap for toxicologists and analysts navigating complex biological evidence.<\/jats:p>","DOI":"10.3390\/toxics13100867","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T14:04:02Z","timestamp":1760537042000},"page":"867","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Analytical Methods for the Determination of Diamorphine (Heroin) in Biological Matrices: A Review"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4488-2194","authenticated-orcid":false,"given":"Ahmed Ibrahim","family":"Al-Asmari","sequence":"first","affiliation":[{"name":"Special Toxicological Analysis Section, Pathology and Laboratory Medicine Division, King Faisal Special Hospital and Research Center, P.O. Box 3354, Riyadh 11211, Saudi Arabia"},{"name":"Faculty of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1093\/jat\/34.4.177","article-title":"Method for the quantification of diamorphine and its metabolites in pediatric plasma samples by liquid chromatography-tandem mass spectrometry","volume":"34","author":"Anderson","year":"2010","journal-title":"J. Anal. Toxicol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1002\/dta.2244","article-title":"Confirmation of recent heroin abuse: Accepting the challenge","volume":"10","author":"Maas","year":"2018","journal-title":"Drug Test. 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