Chiral capillary electrophoretic determination of the enantiomeric purity of homocamptothecin derivatives, promising antitumor topoisomerase I inhibitors, using highly sulfated CDs and fluorescence detection.
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 beta-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-beta-CD, an applied field of 0.2 kV/cm and a fused capillary temperature control of 30 +/- 0.1 degrees C (typical current approximately 175 microA); 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-beta-CD, an applied field of 0.15 kV/cm and a fused capillary temperature control of 25 +/- 0.1 degrees C (typical current approximately 45 muA), 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.
Goossens
Jean-François
JF
Laboratoire de Chimie Analytique, Faculté des Sciences Pharmaceutiques et Biologiques, Université de Lille 2, Lille, France. jean-francois.goossens@univ-lille2.fr
Mahieu
Christine
C
Dias
Nathalie
N
Bailly
Christian
C
Principe
Paola
P
Bonte
Jean-Paul
JP
Lansiaux
Amélie
A
Vaccher
Claude
C
Foulon
Catherine
C
D000970:Antineoplastic Agents / Q000302:isolation & purification*; D002021:Buffers; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000302:isolation & purification; D019075:Electrophoresis, Capillary / Q000379:methods*; D004791:Enzyme Inhibitors / Q000302:isolation & purification*; D013050:Spectrometry, Fluorescence; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013431:Sulfates / Q000737:chemistry; D013696:Temperature; D059004:Topoisomerase I Inhibitors; D047392:beta-Cyclodextrins / Q000737:chemistry
D000970:Antineoplastic Agents; D002021:Buffers; D004791:Enzyme Inhibitors; D013431:Sulfates; D059004:Topoisomerase I Inhibitors; D047392:beta-Cyclodextrins; C120029:homocamptothecin; D002166:Camptothecin