PhD Scientific Days 2026
Budapest, 16-18 June 2026
Pharmaceutical Sciences and Health Technologies 1.
Enantioseparation of Idelalisib: A Combined CE–NMR Study
Előadó neve
Várnagy, Erzsébet, MSc
Neptune code
G0EFA1
Előadó munkahelye
Department of Pharmacognosy, Semmelweis University
Előadó telefonszáma
+36703561926
Előadó e-mail címe
erzsebet.varnagy98@gmail.com
Az előadás címe
Enantioseparation of Idelalisib: A Combined CE–NMR Study
Szerző(k) neve és munkahelye
Erzsébet Várnagy1,2, Balázs István Urbán3, Balázs Volk4, Gyula Simig4, Krisztina Németh5, Milo Malanga6, Ida Fejős1,2, Szabolcs Béni3
1: Department of Pharmacognosy, Semmelweis University, Üllői út 26, H-1085 Budapest, Hungary
2: Center for Pharmacology and Drug Research & Development, Semmelweis University, Üllői út 26, H-1085 Budapest, Hungary
3: Integrative Health and Environmental Analysis Research Laboratory, Department of Analytical Chemistry, Institute of Chemistry, ELTE Eötvös Loránd University, Pázmány Péter sétány 1/A, H-1117 Budapest, Hungary
4: Directorate of Drug Substance Development, Egis Pharmaceuticals Plc., P.O. Box 100, H-1475 Budapest, Hungary
5: Chemical Biology Research Group, Institute of Organic Chemistry, HUN-REN Research Centre for Natural Sciences, Magyar Tudósok Krt. 2., 1117 Budapest, Hungary
6: CarboHyde Ltd., Berlini u. 47-49, H-1045 Budapest, Hungary
Bemutatás módja
Szóbeli
Szekció
Pharmaceutical Sciences and Health Technologies 1.
Language of the presentation
English
Preferred session
Pharmaceutical Sciences and Health Technologies
Összefoglaló szövege
Introduction
Idelalisib is a marketed chiral anticancer agent with an S-configuration. Regulatory guidelines require monitoring of its R-enantiomer to ensure enantiomeric purity, due to potential pharmacological and safety implications of the distomer. Enantioselective analytical methods are therefore essential for quality control in pharmaceutical production.
Aims
This study aimed to develop a sensitive and robust method for trace-level quantification of the R-enantiomer of idelalisib, enabling reliable detection at impurity levels as low as 0.1%, and to investigate the molecular interactions governing enantiomer discrimination.
Method
Cyclodextrin-mediated capillary electrophoresis (CE) was employed, with systematic screening of cyclodextrin (CD) selectors to optimize enantioresolution. The degree of substitution (DS) of hydroxy-propyl-β-CD (HP-β-CD) was varied, identifying an intermediate DS (~6.8) as optimal. Method parameters were optimized using a Box-Behnken design, and robustness was assessed via a Plackett-Burman design. NMR experiments, including 1H, variable temperature measurements, 19F, NOESY, ROESY, and HOESY, were conducted to study conformational dynamics and host-guest interactions.
Results
The CE method achieved max. Rs 4.3 with favorable migration order, demonstrating excellent linearity, precision, and accuracy in accordance with ICH Q2(R2) guidelines. NMR experiments revealed hindered rotation of the 3-phenyl moiety of idelalisib, highlighting its intrinsic conformational dynamics. Complexation with β-CD and HP-β-CD produced clear diastereomeric differentiation in both 1H and 19F NMR spectra. Site-specific 19F NMR revealed distinct exchange regimes of the diastereomeric complexes. NOESY, ROESY, and HOESY data indicated that β-CD predominantly accommodates the fluorinated aromatic ring, whereas HP-β-CD allows additional interactions with the 3-phenyl moiety.
Conclusion
The developed CD-mediated CE method provides a reliable and sensitive approach for monitoring R-idelalisib at trace levels, may be applicable for pharmaceutical quality control. NMR studies elucidated the molecular basis of enantiomer discrimination, revealing distinct inclusion modes and conformational dynamics that support the observed enantioresolution.
Funding
Funded by Bicyclos No. 101130235, and SE 250+ Excellence PhD Scholarship.
University
Semmelweis University
Supervisor
Szabolcs Béni, Ida Fejős
Publication of my abstract
I do not give consent to the publication of my abstract on the website of the congress.
phd.section.field
in doctoral studies after complex exam (PhD)
Kind
Szabad
Status
elfogadva
Accepted presentation method
szóbeli
Előadás fájl jóváhagyás
nem hagyta jóvá
Előadó
8026
Start
16:00
End
16:10