[Show abstract][Hide abstract] ABSTRACT: 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-β-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-β-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-β-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-β-CD as chiral selector. Host-guest interaction between sibutramine and M-β-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.
Full-text · Article · Mar 2012 · Archives of Pharmacal Research
[Show abstract][Hide abstract] ABSTRACT: An analytical micellar electrokinetic chromatographic method was developed and validated for the determination of the L-enantiomer of nateglinide. Separations were carried out in a 50 μm, 64.5/56 fused-silica capillary. The optimized conditions included 75 mM borate buffer, pH 9.2, containing 50 mM of sodium dodecyl sulfate and 25 mg/mL of methyl-β-cyclodextrin as background electrolyte, an applied voltage of 20 kV and a temperature of 15, UV detector at 210 nm. The assay was validated for the L-enantiomer of nateglinide. The limit of detection and quantification were 0.07 and 0.2% respectively. Intraday precision was ranged between 0.12 and 1.7%. Interday precision ranged between 0.73 and 1.73%. The assay was applied to the determination of the L-enantiomer of nateglinide in pharmaceutical formulations.
No preview · Article · Dec 2010 · Archives of Pharmacal Research
[Show abstract][Hide abstract] ABSTRACT: Stereoisomers of nadolol were derivatized with S-(-)-menthyl chloroformate((-)-MCF) forming their diastereomers, RSR-nadolol-(-)-MCF, SRS-nadolol-(-)-MCF, RRS-nadolol-(-)-MCF and SSRnadolol-(-)-MCF. Diastereomeric mixture were then chromatographically resolved by preparative HPLC (JAIGEL-ODS-BP-L, 500 × 25 mm column) eluted with methanol-water (84:16, v/v) at flow rate 2.5 mL/min. RSR-nadolol-(-)-MCF diastereomer was hydrolyzed with 5% LiOH at 80°C for 48 h, and the decomposed mixture was further purified by semi-preparative HPLC. The purity and final yield of RSR-nadolol were 99.97% and 12.95%, respectively.
Full-text · Article · Sep 2010 · Archives of Pharmacal Research