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Chiral capillary electrophoretic determination of the enantiomeric purity of homocamptothecin derivatives, promising antitumor topoisomerase I inhibitors, using highly sulfated CDs and fluorescence detection
Author(s) -
Goossens JeanFrançois,
Mahieu Christine,
Dias Nathalie,
Bailly Christian,
Principe Paola,
Bonte JeanPaul,
Lansiaux Amélie,
Vaccher Claude,
Foulon Catherine
Publication year - 2006
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.200600143
Subject(s) - chemistry , capillary electrophoresis , enantiomer , chromatography , triethanolamine , fluorescence , detection limit , sulfation , enantiomeric excess , phosphate buffered saline , electrophoresis , analytical chemistry (journal) , stereochemistry , biochemistry , enantioselective synthesis , physics , quantum mechanics , catalysis
EKC methods for the enantiomeric resolution of homocamptothecin derivatives, potent anticancer agents targeting DNA topoisomerase I selected for clinical trials, were developed using highly sulfated β‐CD as chiral selectors at acidic pH. Optimal electrophoretic conditions, with migration times under 15 min, were as follows: for the neutral homocamptothecin analog 1 , a BGE of 75 mM phosphate buffer pH 2.5 (H 3 PO 4 + triethanolamine)/ACN – 95/5 v/v, with 7.5% w/v highly S‐β‐CD, an applied field of 0.2 kV/cm and a fused capillary temperature control of 30 ± 0.1°C (typical current approximately 175 μA); for the cationic homocamptothecin 2 , a BGE of 25 mM phosphate buffer pH 2.5 (H 3 PO 4 + TEA)/ACN – 90/10 v/v, with 2.5% w/v highly S‐β‐CD, an applied field of 0.15 kV/cm and a fused capillary temperature control of 25 ± 0.1°C (typical current approximately 45 μA), and both are validated. The best results in terms of LOQ were obtained by EC with fluorescence detection: 10 ng/mL and 20 ng/mL for 1 and 2 , respectively (LOQ divided by 150 for 1 and 5 for 2 with respect to UV), thus making this method particularly convenient for enantiomeric purity determination of galenic forms. UV detection appears to be an alternative to fluorescence for the analysis of the main component either for the control of galenic forms or for therapeutic adaptation. Moreover, this method exhibits better performances than HPLC.