{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T05:15:12Z","timestamp":1783401312036,"version":"3.54.6"},"reference-count":36,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union\u2019s Horizon Europe research and innovation program under the Marie Sklodowska-Curie grant agreement Bicyclos","award":["N\u25e6 101130235"],"award-info":[{"award-number":["N\u25e6 101130235"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Idelalisib (IDE) is a marketed chiral anticancer drug administered as the S-enantiomer, requiring sensitive monitoring of the R-enantiomer to ensure enantiomeric purity. However, no dedicated capillary electrophoresis (CE) method has been reported for trace-level quantification of R-IDE. In this study, a cyclodextrin-mediated CE method was developed for reliable detection of the R-enantiomer at the 0.1% level (LOD 2 \u00b5g\/mL; LOQ 5 \u00b5g\/mL). Systematic screening identified hydroxypropyl-\u03b2-cyclodextrin (HP-\u03b2-CD) with an intermediate degree of substitution (DS~6.8) as the optimal chiral selector, providing efficient enantioseparation (Rs up to 4.3). The method was validated according to ICH Q2(R2) guidelines, demonstrating suitable precision, accuracy, and robustness. Complementary NMR studies revealed hindered rotation of the 3-phenyl moiety and elucidated the molecular basis of enantioselectivity. Complexation with \u03b2-CD and HP-\u03b2-CD produced clear diastereomeric differentiation in both 1H and 19F NMR spectra, while the simplified 19F NMR profiles enabled direct enantiomer discrimination. NOESY and ROESY experiments demonstrated distinct inclusion modes, with HP-\u03b2-CD accommodating both the fluorinated aromatic ring and the 3-phenyl moiety. These interactions may account for the superior enantioseparation observed with HP-\u03b2-CD of intermediate DS. Our validated CE method addresses the distomer determination while NMR insights provide mechanistic understanding of the chiral recognition.<\/jats:p>","DOI":"10.3390\/ijms27136036","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:43:14Z","timestamp":1783345394000},"page":"6036","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cyclodextrin-Mediated Enantiomeric Separation of Idelalisib: A Validated Capillary Electrophoresis and NMR Study"],"prefix":"10.3390","volume":"27","author":[{"given":"Erzs\u00e9bet","family":"V\u00e1rnagy","sequence":"first","affiliation":[{"name":"Department of Pharmacognosy, Semmelweis University, \u00dcll\u0151i \u00fat 26, H-1085 Budapest, Hungary"},{"name":"Center for Pharmacology and Drug Research & Development, Semmelweis University, \u00dcll\u0151i \u00fat 26, H-1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bal\u00e1zs Istv\u00e1n","family":"Urb\u00e1n","sequence":"additional","affiliation":[{"name":"Integrative Health and Environmental Analysis Research Laboratory, Department of Analytical Chemistry, Institute of Chemistry, ELTE E\u00f6tv\u00f6s Lor\u00e1nd University, P\u00e1zm\u00e1ny P\u00e9ter S\u00e9t\u00e1ny 1\/A, H-1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e1ty\u00e1s","family":"S\u00e1ri","sequence":"additional","affiliation":[{"name":"Integrative Health and Environmental Analysis Research Laboratory, Department of Analytical Chemistry, Institute of Chemistry, ELTE E\u00f6tv\u00f6s Lor\u00e1nd University, P\u00e1zm\u00e1ny P\u00e9ter S\u00e9t\u00e1ny 1\/A, H-1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2019-1874","authenticated-orcid":false,"given":"Bal\u00e1zs","family":"Volk","sequence":"additional","affiliation":[{"name":"Directorate of Drug Substance Development, Egis Pharmaceuticals Plc., P.O. Box 100, H-1475 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2569-6476","authenticated-orcid":false,"given":"Gyula","family":"Simig","sequence":"additional","affiliation":[{"name":"Directorate of Drug Substance Development, Egis Pharmaceuticals Plc., P.O. Box 100, H-1475 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1360-7648","authenticated-orcid":false,"given":"Krisztina","family":"N\u00e9meth","sequence":"additional","affiliation":[{"name":"Chemical Biology Research Group, Institute of Organic Chemistry, HUN-REN Research Centre for Natural Sciences, Magyar Tud\u00f3sok Krt. 2, H-1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Milo","family":"Malanga","sequence":"additional","affiliation":[{"name":"CarboHyde Ltd., Berlini u. 47-49, H-1045 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3458-0854","authenticated-orcid":false,"given":"Ida","family":"Fej\u0151s","sequence":"additional","affiliation":[{"name":"Department of Pharmacognosy, Semmelweis University, \u00dcll\u0151i \u00fat 26, H-1085 Budapest, Hungary"},{"name":"Center for Pharmacology and Drug Research & Development, Semmelweis University, \u00dcll\u0151i \u00fat 26, H-1085 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7056-6825","authenticated-orcid":false,"given":"Szabolcs","family":"B\u00e9ni","sequence":"additional","affiliation":[{"name":"Integrative Health and Environmental Analysis Research Laboratory, Department of Analytical Chemistry, Institute of Chemistry, ELTE E\u00f6tv\u00f6s Lor\u00e1nd University, P\u00e1zm\u00e1ny P\u00e9ter S\u00e9t\u00e1ny 1\/A, H-1117 Budapest, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,5]]},"reference":[{"key":"ref_1","unstructured":"(2026, March 11). 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