Determination of the R-enantiomer of valsartan in pharmaceutical formulation by capillary electrophoresis.

Capillary zone electrophoresis was successfully applied to the enantiomeric purity determination of valsartan using acetyl-ß-cyclodextrin (A-ß-CD) as a chiral selector. Separations were carried out in a 50 µm, 64/56 cm fused-silica capillary. The optimized conditions included 25 mM phosphate buffer, pH 8.0, containing 10 mM A-ß-CD as background electrolyte, an applied voltage of +30 kV and a temperature of 30 °C. Ibuprofen was used as an internal standard. The assay was validated for the R-enantiomer of valsartan in the range of 0.05-3.0%. The limit of detection was 0.01%, the limit of quantitation was 0.05%, relative to a concentration of valsartan of 1 mg/ml. Intra-day precision varied between 2.57 and 5.60%. Relative standard deviations of inter-day precision ranged between 4.46 and 6.76% for peak area ratio. The percentage recovery of the R-enantiomer of valsartan ranged between 97.0 and 99.6% in valsartan product. The assay was applied to the determination of the chiral purity of valsartan tablets and R-enantiomer of valsartan was found as an impurity.

Chiral discrimination of sibutramine enantiomers by capillary electrophoresis and proton nuclear magnetic resonance spectroscopy.

Capillary electrophoresis (CE) and proton nuclear magnetic resonance spectroscopy ((1)H-NMR) have been used to discriminate the enantiomers of sibutramine using cyclodextrin derivatives. Possible correlation between CE and (1)H-NMR was examined. Good correlation between the (1)H-NMR shift non-equivalence data for sibutramine and the degree of enantioseparation in CE was observed. In CE study, a method of enantiomeric separation and quantitation of sibutramine was developed using enantiomeric standards. The method was based on the use of 50 mM of phosphate buffer of pH 3.0 with 10 mM of methyl-beta-cyclodextrin (M-ß-CD). 0.05% of LOD, 0.2% of LOQ for S-sibutramine enantiomer was achieved, and the method was validated and applied to the quantitative determination of sibutramine enantiomers in commercial drugs. On a 600 MHz (1)H-NMR analysis, enantiomer signal separation of sibutramine was obtained by fast diastereomeric interaction with a chiral selector M-ß-CD. For chiral separation and quantification, N-methyl proton peaks (at 2.18 ppm) were selected because of its being singlet and simple for understanding of diastereomeric interaction. Effects of temperature and concentration of chiral selector on enantiomer signal separation were investigated. The optimum condition was 0.5 mg/mL of sibutramine and 10 mg/mL of M-ß-CD at 10°C. Distinguishment of 0.5% of S-sibutramine in R-sibutramine was found to be possible by (1)H-NMR with M-ß-CD as chiral selector. Host-guest interaction between sibutramine and M-ß-CD was confirmed by (1)H-NMR studies and CE studies. A Structure of the inclusion complex was proposed considering (1)H-NMR and 2D ROESY studies.