Application of Guanidine Hcl to Improve Enantioseparation of a Model Basic Drug, Cetirizine, By Capillary Electrophoresis Using Sulfated Β-Cyclodextrin

Document Type : Research article

Authors

1 Pharmaceutical Chemistry Depratment, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Pharmaceutical Chemistry Depratment, School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Abstract

A common approach in resolving enantiomers of chiral basic drugs by capillary electrophoresis (CE) is to use cyclodextrins (especially their anionic derivatives) as chiral selector in the acidic buffer (pH ≤ 3) in normal or reversed (carrier) mode. Then, some organic modifiers are added to the buffer solution if the resolution is not satisfactory. In case of cetirizine (CTN), applying the same approach, i.e. a reversed mode capillary zone electrophoresis (CZE) method with an acidic buffer and sulfated-b-cyclodextrine (S-bCD) as chiral selector, was failed and no complete enantioseparation was achieved. Different organic modifiers, like urea and triethylamine HCl, were used to improve chiral resolution which led to partial resolution of the two peaks. Then, guanidine HCl at a concnetration of 100 mM was added to the running buffer and an acceptable resolution of the enantiomers of the drug was obtained. The method was successfully applied to determine optical purity of a levo-cetirizine (l-CTN) sample.

Keywords

Main Subjects


Eeckhaut AV and Michotte Y. Chiral Separations by
Capillary Electrophoresis
. CRC Press (Taylor and
Francis Group), Boca Raton FL (2010) 1.

Ahuja S and Jimidar MI.
Capillary Electrophoresis
Methods for Pharmaceutical Analysis
. Academic
Press, Verlag (2008) 529.

Gübitz G and Schmid MG. Chiral separation by

capillary electromigration techniques.
J. Chromatogr.
A
(2008) 1204: 140–56.
Scriba GKE. Fundamental aspects of chiral

electromigration techniques and application in

pharmaceutical and biomedical analysis
. J. Pharm.
Biomed. Anal.
(2011) 55: 688–701.
Fanali S. Enantioselective determination by capillary
electrophoresis with cyclodextrins as chiral selectors
.
J. Chromatogr. A
(2000) 875: 89–122.
Chankvetadze B. Enantioseparations by using capillary

electrophoretic techniques: The story of 20 and a few

more years.
J. Chromatogr. A (2007) 1168: 45–70
Weinberger R
. Practical Capillary Electrophoresis .
2
nd ed. Academic Press, San Diego, Chap. 2, (2000) 37.
Eeckhaut AV, Detaevernier MR, Crommen

J and Michotte Y. Influence of methanol on

the enentioresolution of antihistamine with

carboxymethyl-β- cyclodextrin in capillary

electrophoresis.
Electrophoresis (2004) 25: 2838–47.
Noumie Surugau L, Bergström ET and Goodall DM.

Effects of organic solvent and cationic additive on

capillary electrophoresis of peptides.
Malaysian J.
Anal. Sci.
(2008) 12: 520-7.
Terabe S, Ishihama Y, Nishi H, Fukuyama T and Otsuka

K. Effect of urea addition in micellar electrokinetic

chromatography
. J. Chromatogr. A (1991) 545: 359-
68.

Garcia-Ruiz C, Crego AL and Marina ML. Comparison

of charged cyclodextrin derivatives for the chiral

separation of atropisomeric polychlorinated biphenyls

by capillary electrophoresis.
Electrophoresis (2003)
24: 2657-64.

Lie DR (ed).
CRC Handbook of Chemistry and Physics.
84
th ed., CRC Press, Boca Rotan (2003) Sect. 8.
Zand Karimi M, Shafaati A, Foroutan SM and

Hassani Oliaee N. Separation of tramadol enantiomers

by capillary electrophoresis using highly sulfated

cyclodextrins.
DARU (2005) 13: 143-7.
Zandkarimi M, Shafaati A and
Foroutan SM. Chiral
separation of basic and zwitterionic drugs by HSCD

using CE.
Iran. J. Pharm. Res. (2008) 7: 275-83.
Zandkarimi M, Shafaati A,
Foroutan SM and Lucy
CA. Improvement of electrophoretic enantioseparation

of amlodipine by polybrene.
Iran. J. Pharm. Res.
(2012) 11: 129-36.

Sattary Javid F,
Shafaati A and Zarghi A.
Determination of cetirizine and its impurities in bulk

and tablet formulation using a validated capillary zone

electrophoretic method
. J. Anal. Chem. (2014) 69:
442-7.
Gillard M, Perren CVD, Mogulevsky N, Massingham
R and Chatelain P. Binding characteristics of cetirizine

and levocetirizine to human H1 histamine receptors:

Contribution of Lys
191 and Thr194 . Mol. Pharmacol.
(2002) 61: 391-9.

Bailey PJ and Pace S. The coordination chemistry

of guanidines and guanidinates.
Coord. Chem. Rev.
(2001) 214: 91–141.

Scriba GKE. Cyclodextrins in capillary electrophoresis

enantioseparations Recent developments and

applications
. J. Sep. Sci. (2008) 31: 1991–2011.
Wren SAC and Rowe RC. Theoretical aspects of

chiral separation in capillary electrophoresis: I. Initial

evaluation of a model.
J. Chromatogr. A (1992) 603:
235-43.

Owens PK, Fell AF, Coleman MW and Berridge JC.

Effect of charged and uncharged chiral additives on

the resolution of amlodipine enantiomers in liquid

chromatography and capillary electrophoresis.
J.
Chromatogr. A
(1998) 797: 187-95.
Chen C. Physicochemical, pharmacological and

pharmacokinetic properties of the zwitterionic

antihistamines cetirizine and levocetirizine.
Curr.
Med. Chem
. (2008) 15: 2173-91.
Mikuš P, Valášková I and Emil H. Enantioselective

analysis of cetirizine in pharmaceuticals by

cyclodextrin-mediated capillary electrophoresis
. J.
(17)

(18)

(19)

(20)

(21)

(22)

(23)

Sep. Sci.
(2005) 28: 1278-84.
Eeckaut AV and Michotte Y. Chiral separation of

cetirizine by capillary electrophoresis.
Electrophoresis
(2006) 27: 2376-85.

Sekhon BS. Enantioseparation of chiral drugs-an

overview.
Int. J. Pharm. Tech. Res. (2010) 2: 1584-94.
Rizzi A. Fundamental aspects of chiral separations by

capillary electrophoresis.
Electrophoresis (2001) 22:
3079-106.

Rudaz S, Calleri E, Geiser L, Cherkaoui S, Prat J

and Veuthey JL. Infinite enantiomeric resolution of

basic coumpounds using highly sulfated cyclodextrin

as chiral selector in capillary electrophoresis
.
Electrophoresis
(2003) 24: 2633-41.
Gobbi A and Frenking G. Y-Conjugated compounds:

the equilibrium geometries and electronic structures

of guanidine, guanidinium cation, urea, and

1,1-diaminoethylene
. J. Am. Chem. Soc. (1993) 115:
2362-72.

Ki Lim W, Rösgen J and Englander SW. Urea, but

not guanidinium, destabilizes proteins by forming

hydrogen bonds to the peptide.
Proc. Natl. Acad. Sci.
U.S.A.
(2009) 106: 2595-600.
International Conference on Harmonization (ICH).

Validation of Analytical Procedures: Text and

Methodology Q2(R1)
. Geneva, Switzerland (2005).