title: Chiral discrimination of sibutramine enantiomers by capillary electrophoresis and proton nuclear magnetic resonance spectroscopy.
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.
authors.affiliation: College of Pharmacy, Kangwon National University, Chuncheon, 200-701, Korea.
authors.forename: Yong-Jae
authors.initials: YJ
authors.lastname: Lee
authors.forename: Seungho
authors.initials: S
authors.lastname: Choi
authors.forename: Jinhoo
authors.initials: J
authors.lastname: Lee
authors.forename: NgocVan Thi
authors.initials: NT
authors.lastname: Nguyen
authors.forename: Kyungran
authors.initials: K
authors.lastname: Lee
authors.forename: Jong Seong
authors.initials: JS
authors.lastname: Kang
authors.forename: Woongchon
authors.initials: W
authors.lastname: Mar
authors.forename: Kyeong Ho
authors.initials: KH
authors.lastname: Kim
mesh_terms: D002138:Calibration; D003503:Cyclobutanes / Q000737:chemistry / Q000302:isolation & purification*; D019075:Electrophoresis, Capillary / Q000379:methods*; D057230:Limit of Detection; D016014:Linear Models; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D015394:Molecular Structure; D011522:Protons; D012015:Reference Standards; D015203:Reproducibility of Results; D013237:Stereoisomerism; D047392:beta-Cyclodextrins / Q000737:chemistry
chemical_list: D003503:Cyclobutanes; D011522:Protons; D047392:beta-Cyclodextrins; C108732:methyl-beta-cyclodextrin; C058254:sibutramine