Enantioselective determination of S-(+)- and R-(-)-ondansetron in human serum using derivatized cyclodextrin-modified capillary electrophoresis and solid-phase extraction.
A high-performance capillary electrophoresis (HPCE) assay method for the quantitation of S-(+)- and R-(-)-ondansetron in human serum was developed. Resolution was achieved using 15 mM heptakis-(2, 6-di-O-methyl)-beta-cyclodextrin (DM-beta-CD) in 100 mM phosphate buffer (pH 2.5). A 72-cm untreated fused-silica capillary, at a constant voltage of 20 kV, was used for the analysis. A 0.03-mM cationic detergent was used as a buffer additive to decrease the adsorption of endogenous substances onto the silica wall. The analytes of interest were isolated from endogenous substances using a solid-phase extraction procedure. The cyanopropyl cartridge gave good recoveries in excess of 85% for both S-(+)- and R-(-)-ondansetron, without any interferences. To decrease the limits of detection of the analytes, an on-capillary sample concentration technique was employed. The detection limit was 10 ng/ml using 2 ml of serum and the limit of quantitation was 15 ng/ml. The calibration curve was linear over a range of 15-250 ng/ml, with procainamide as the internal standard, and the coefficients of determination obtained were greater than 0.999 (n = 3). Precision and accuracy of the method were 2.76-5.80 and 2.10-5.00%, respectively, for S-(+)-ondansetron, and 3.10-6.57 and 2.50-4.35%, respectively, for R-(-)-ondansetron. The HPCE method is a useful alternative to existing chiral high-performance liquid chromatographic methods.
Siluveru
M
M
Department of Medicinal Chemistry, College of Pharmacy, University of Georgia, Athens 30602-2352, USA.
Stewart
J T
JT
D000932:Antiemetics / Q000097:blood*; D003505:Cyclodextrins; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D016014:Linear Models; D015394:Molecular Structure; D017294:Ondansetron / Q000097:blood* / Q000737:chemistry; D012680:Sensitivity and Specificity; D012702:Serotonin Antagonists / Q000097:blood*; D013237:Stereoisomerism
D000932:Antiemetics; D003505:Cyclodextrins; D012702:Serotonin Antagonists; D017294:Ondansetron