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Isoindole formation has been used effectively for the fluorescence detection of a wide range of analytes, including aliphatic and aromatic primary amines, amino acids, some proteins, thiols, cyanides, and others. Such derivatization is flexible and can be tailored for the analysis of different classes of compounds using techniques such as direct spectrofluorimetry, HPLC, and capillary electrophoresis. Most of the isoindole formation reactions proceeded rapidly at room temperature and yielded highly fluorescent products without the generation of interfering by\u2010products. Several alternative reagents for the formation of isoindoles have also emerged; however, o\u2010phthaldehyde is still the most commonly used reagent. The advantages and potential applications of these alternatives were discussed. Overall, this review will enlighten researchers on the development and applicability of o\u2010phthaldehyde analogs based on isoindole formation in quantitative analysis and detection of biomolecular targets.<\/jats:p>","DOI":"10.1002\/bio.70419","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T14:39:58Z","timestamp":1767883198000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["O\u2010Phthaldehyde Analogs as Isoindole Forming Probes: A Versatile Fluorimetric Approach for Biomedical and Pharmaceutical Analysis\u2014A Critical Review"],"prefix":"10.1002","volume":"41","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6456-1104","authenticated-orcid":false,"given":"Sayed\u00a0M.","family":"Derayea","sequence":"first","affiliation":[{"name":"Pharmaceutical Analytical Chemistry Department, Faculty of Pharmacy Minia University  Minia Egypt"},{"name":"Pharmaceutical Analytical 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