title: Determination of trace amount of enantiomeric impurity in therapeutic nicotine derivative using capillary electrophoresis with new imaging technology detection.
abstract: One of the many attempts to stop the danger of tobacco smoking is the development of an anti-smoking vaccine using nicotine butyric acid (NBA) linked to a carrier protein to produce anti-nicotine antibodies. NBA is a chiral molecule and there is a need to obtain a high degree of enantiomeric purity. The aim of this work is to develop a novel method for the enantioseparation of NBA and the determination of trace amounts of enantiomeric impurity required by regulatory authorities. This was achieved successfully using high-performance capillary electrophoresis combined with label-free intrinsic imaging as new imaging technology. A 50 μm id fused-silica capillary was used with UV detection at λ(214 ) nm and label-free intrinsic imaging. The background electrolyte consisted of highly sulphated β-cyclodextrin 10% m/V as a chiral selector in 75 mM phosphoric acid-triethylamine at pH 7.0. Baseline separation and detection of 0.1% and possibly less of the unwanted impurity (R-enantiomer) were achieved. Also, the detection limits were calculated for both enantiomers. The use of label-free intrinsic imaging has improved the sensitivity, enabling us to detect trace amounts of enantiomeric impurities.
authors: Microseparation Group, Pharmaceutical Science Research Division, King's College London, London, UK. ali.aboel_dahab@kcl.ac.uk
authors: Ali A
authors: AA
authors: Dahab
authors: Norman W
authors: NW
authors: Smith
mesh_terms: D020148:Butyric Acid / Q000737:chemistry* / Q000627:therapeutic use; D004340:Drug Contamination / Q000517:prevention & control*; D019075:Electrophoresis, Capillary / Q000295:instrumentation / Q000379:methods*; D006801:Humans; D009538:Nicotine / Q000737:chemistry* / Q000627:therapeutic use; D013237:Stereoisomerism; D014029:Tobacco Use Disorder / Q000188:drug therapy*
chemical_list: D020148:Butyric Acid; D009538:Nicotine