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.

Racemisation in Chemistry and Biology

“…Although most biological racemisations take place in aqueous conditions, the racemisation of one molecule (nicotine, 27; Figure8)u nder extreme heatinga nd in the vapour phase has received ag reat deal of attention.I n normal tobacco, 27 is predominantly the S enantiomer with estimates ranging from 0.03 %t oa bout 0.2 to 0.3 %o fR-27 present. [65][66][67] However, in tobacco smoke, this increases to about3%. The variation between tobacco types was studied by GCMS and it was found that the R enantiomer was consistently below 0.5 %o ft otal 27 in eight different brandsa nd then 2.6-3.6 %i nt he smoke.…”

“…Although most biological racemisations take place in aqueous conditions, the racemisation of one molecule (nicotine, 27 ; Figure ) under extreme heating and in the vapour phase has received a great deal of attention. In normal tobacco, 27 is predominantly the S enantiomer with estimates ranging from 0.03 % to about 0.2 to 0.3 % of R ‐ 27 present . However, in tobacco smoke, this increases to about 3 %.…”

Application of cyclodextrins in chiral capillary electrophoresis

“…Sulfated ␤-CD Amlodipine [241], Betti bases [300], borreverine [259], bupivacaine [178], 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone [283], cetirizine [91,301], citalopram [97], hydroxyflavanones [324], fluoxetine [302], helquats [293,303], 4,5-disubstituted imidazoles [304], lorazepam [108,162], 3-hydroxymexiletine [305], modafinil [134,306], nicotine and its related compounds [307], nicotine butyric acid [90], ofloxacin and ornidazole [132], 3,4-dihydroxyphenylalanine [238,[308][309][310], phenylalanine [308], isoprenaline [92], rotigotine and related chiral impurities [252], thioridazine [311], tolterodine and methoxytolterodine [89], tryptophan [312], tyrosine [238,308], benzoxazolinonic aminoalcohols [294], 13 new amphetamine-like designer drugs [313], 12 basic analytes [314], 19 cathinone derivatives [315], impurity of clopidogrel [316], four antimalarial drugs [280], four basic drugs [295], five basic drugs [296], six basic drugs…”

Chiral selectors in CE: Recent developments and applications (2012‐mid 2014)

“…Different amphetamine‐like drugs were enantioseparated by using different S‐β‐CD concentrations each time (1–10 mg/mL). It is worth pointing out that there are also more reports regarding the use of S‐β‐CD and highly sulfated‐β‐CD (HS‐β‐CD) as CSs for the enantioseparation of several drugs and clinically important compounds, such as tolterodine and methoxytolterodine , escitalopram , verapamil, norverapamil , cathinone derivatives , and nicotine butyric acid .…”