{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T09:28:29Z","timestamp":1777627709896,"version":"3.51.4"},"reference-count":34,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T00:00:00Z","timestamp":1774915200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2026,6,30]]},"abstract":"ABSTRACT<\/jats:title>\n \n Rationale<\/jats:title>\n \n Chromatographic and electrophoretic methods reliably distinguish the heterozygous and homozygous sickle cell states with hemoglobin variants appearing at consistent percentages with specific retention or migration times. However, co\u2010migrating variants alter the overall hemoglobin profile, complicating interpretation in compound heterozygous conditions such as \u03b2\n S<\/jats:sup>\n \/\u03b2\n D\u2010Punjab<\/jats:sup>\n since these variants electrophoretically migrate close to each other. These cases often require hematological correlation or molecular confirmation. As molecular testing is not available in all laboratories, mass spectrometry (MS) may serve as an alternate approach for examining complex compound heterozygous sickle cell disorders.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n Hemoglobin extracted from K2 EDTA blood samples (\n n<\/jats:italic>\n \u2009=\u2009154) was analyzed using flow\u2010injection triple quadrupole MS. Summed intensities of three charge states each of \u03b2\n S<\/jats:sup>\n and \u03b2 globin monomers enabled calculation of the \u03b2\n S<\/jats:sup>\n \/\u03b2 ratio to differentiate sickle cell trait (SCT) from sickle cell disease (SCD). Additional globin ratios (\u03b1\/\u03b2, \u03b3\/\u03b2, \u03b4\/\u03b1 (%)) were evaluated to subclassify SCD into Group 1 (\u03b2\n S<\/jats:sup>\n \u03b2\n E<\/jats:sup>\n , \u03b2\n S<\/jats:sup>\n \u03b2\n D\u2010Punjab<\/jats:sup>\n , \u03b2\n S<\/jats:sup>\n \u03b2\n C<\/jats:sup>\n , \u03b2\n S<\/jats:sup>\n Lepore\u2010BW), Group 2 (\u03b2\n S<\/jats:sup>\n \u03b2\n 0<\/jats:sup>\n ), and Group 3 (\u03b2\n S<\/jats:sup>\n \u03b2\n S<\/jats:sup>\n ). Statistical analysis was performed using SPSS v27.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n The \u03b2\n S<\/jats:sup>\n \/\u03b2 ratio effectively differentiated SCT from SCD with an optimal cut\u2010off value of 0.71 yielding 90.3% sensitivity and 98.4% specificity. The ratios \u03b1\/\u03b2, \u03b3\/\u03b2, \u03b4\/\u03b1 (%), \u03b2\n S<\/jats:sup>\n \/\u03b2, significantly discriminated against Group 1 from Group 3 (\n p<\/jats:italic>\n \u2009<\u20090.001). While \u03b3\/\u03b2 ratio significantly differentiated Group 1 from Group 2 (\n p<\/jats:italic>\n \u2009<\u20090.001), the \u03b4\/\u03b1 (%) ratio was superior for distinguishing Group 2 from Group 3 (\n p<\/jats:italic>\n \u2009<\u20090.001).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n A rapid, cost\u2010effective MS approach distinguishes SCT from SCD while \u03b3\/\u03b2 and \u03b4\/\u03b1 (%), ratios refine SCD subclassification alongside \u03b2\n S<\/jats:sup>\n \/\u03b2. Combined with capillary electrophoresis (CE), this approach enhances diagnostic resolution and may reduce the need for molecular testing.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/rcm.70067","type":"journal-article","created":{"date-parts":[[2026,4,1]],"date-time":"2026-04-01T01:25:22Z","timestamp":1775006722000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Decoding Sickle Cell Disorders Using Flow Injection Analysis Mass Spectrometry"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4717-1523","authenticated-orcid":false,"given":"Deepalakshmi\u00a0D.","family":"Putchen","sequence":"first","affiliation":[{"name":"R&D, Neuberg Anand Academy of Laboratory Medicine Pvt Ltd Bengaluru 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