title: Separation strategy for acidic chiral pharmaceuticals with capillary electrochromatography on polysaccharide stationary phases.
abstract: The effect of five factors on the capillary electrochromatographic enantioseparation of acidic compounds was studied using an experimental design. The studied factors were pH, acetonitrile content in the mobile phase, temperature, buffer concentration, and applied voltage. These experiments allowed defining a generic separation strategy applicable on acidic compounds with chemical and structural diversity. The starting screening conditions consist of a 45 mM ammonium formate electrolyte at pH 2.9 mixed with 65% acetonitrile, an applied voltage of 15 kV, and a temperature of 25 degrees C. The screening phase occasionally can be followed by an optimization procedure. Evaluation of the proposed strategy pointed out that it allows achieving baseline resolution within a relatively short time when a beginning of separation is obtained at the starting conditions. This strategy revealed enantioselectivity for 11 compounds out of 15, of which 10 could be baseline-separated after the proposed optimization steps.
authors.affiliation: Department of Pharmaceutical and Biomedical Analysis, Pharmaceutical Institute, Vrije Universiteit Brussel-VUB, Brussels, Belgium.
authors.forename: Debby
authors.initials: D
authors.lastname: Mangelings
authors.affiliation: Department of Pharmaceutical and Biomedical Analysis, Pharmaceutical Institute, Vrije Universiteit Brussel-VUB, Brussels, Belgium.
authors.forename: Indiana
authors.initials: I
authors.lastname: Tanret
authors.affiliation: Department of Pharmaceutical and Biomedical Analysis, Pharmaceutical Institute, Vrije Universiteit Brussel-VUB, Brussels, Belgium.
authors.forename: Nele
authors.initials: N
authors.lastname: Matthijs
authors.affiliation: Discovery Analytical Department, Sanofi-Synthelabo Recherche, Toulouse, France.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Maftouh
authors.forename: D Luc
authors.initials: DL
authors.lastname: Massart
authors.affiliation: Department of Pharmaceutical and Biomedical Analysis, Pharmaceutical Institute, Vrije Universiteit Brussel-VUB, Brussels, Belgium.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Vander Heyden
mesh_terms: D000097:Acetonitriles; D002021:Buffers; D020374:Chromatography, Micellar Electrokinetic Capillary / Q000379:methods*; D019075:Electrophoresis, Capillary; D005480:Flurbiprofen / Q000302:isolation & purification; D006591:Hexobarbital / Q000302:isolation & purification; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000302:isolation & purification; D004364:Pharmaceutical Preparations / Q000302:isolation & purification*; D011134:Polysaccharides; D013237:Stereoisomerism; D013696:Temperature; D014859:Warfarin / Q000302:isolation & purification
chemical_list: D000097:Acetonitriles; D002021:Buffers; D004364:Pharmaceutical Preparations; D011134:Polysaccharides; D005480:Flurbiprofen; D014859:Warfarin; D006591:Hexobarbital; D007052:Ibuprofen; C032159:acetonitrile
references.citation: Fassihi, A. R., Int. J. Pharmaceutics 1993, 92, 1-14.
references.citation: Maier, N. M, Franco, P., Lindner, W., J. Chromatogr. A 2001, 906, 3-33.
references.citation: Agranat, I., Caner, H., Caldwell, J., Nat. Rev. Drug Discov. 2002, 1, 753-768.
references.citation: Caner, H., Groner, E., Levy, L., Agranat, I., Drug Discovery Today 2004, 9, 105-110.
references.citation: De Camp, W. H., J. Pharm. Biomed. Anal. 1993, 11, 1167-1172.
references.citation: Williams, R. C., Riley, C. M., Sigvardson, K. W., Fortunak, J., Ma, P., Nicolas, E. C., Unger, S. E., Krahn, D. F., Bremner, S. L., J. Pharm. Biomed. Anal. 1998, 17, 917-924.
references.citation: FDA's policy statement for the development of new stereisomeric drugs, US Food and Drug Administration 1992 (on-line): http://www.fda.gov/cder/guidance/stereo.htm
references.citation: Aires-de-Sousa, J., Gasteiger, J., J. Mol. Graphics Modelling 2002, 20, 373-388.
references.citation: Booth, T. D., Azzaoui, K., Wainer, I. W., Anal. Chem. 1997, 69, 3879-3883.
references.citation: Suzuki, T., Timofei, S., Iuoras, B. E., Uray, G., Verdino, P., Fabian, W. M. F., J. Chromatogr. A 2001, 922, 13-23.
references.citation: Matthijs, N., Perrin, C., Maftouh, M., Massart, D. L., Vander Heyden, Y., J. Chromatogr. A 2004, 1041, 119-133.
references.citation: Tachibana, K., Ohnishi, A., J. Chromatogr. A 2001, 906, 127-154.
references.citation: Matthijs, N., Perrin, C., Maftouh, M., Massart, D. L., Vander Heyden, Y., J. Pharm. Biomed. Anal. 2002, 27, 515-529.
references.citation: Rizzi, A., Electrophoresis 2001, 22, 3079-3106.
references.citation: Chankvetadze, B., Blaschke, G., J. Chromatogr. A 2001, 906, 309-363.
references.citation: Schurig, V., J. Chromatogr. A 2001, 906, 275-299.
references.citation: Borman, P., Boughtflower, B., Cattanach, K., Crane, K., Freebairn, K., Jonas, G., Mutton, I., Patel, A., Sanders, M., Thompson, D., Chirality 2003, 15, S1- S12.
references.citation: Liu, Y., Berthod, A., Mitchell, C. R., Ling Xiao, T., Zhang, B., Armstrong, D. W., J. Chromatogr. A 2002, 978, 185-204.
references.citation: Fanali, S., Catarcini, P., Blaschke, G., Chankvetadze, B., Electrophoresis 2001, 22, 3131-3151.
references.citation: Girod, M., Chankvetadze, B., Blaschke, G., J. Chromatogr. A 2000, 887, 439-455.
references.citation: Tobler, E., Lämmerhofer, M., Lindner, W., J. Chromatogr. A 2000, 875, 341-352.
references.citation: Fanali, S., Catarcini, P., Presutti, C., J. Chromatogr. A 2003, 994, 227-232.
references.citation: Karlsson, C., Karlsson, L., Armstrong, D. W., Owens, P. K., Anal. Chem. 2000, 72, 4394-4401.
references.citation: Zheng, J., Shamsi, S. A., J. Chromatogr. A 2003, 1005, 177-187.
references.citation: Okamoto, Y., Kaida, Y., J. Chromatogr. A 1994, 666, 403-419.
references.citation: Mangelings, D., Hardies, N., Maftouh, M., Suteu, C., Massart, D. L., Vander Heyden, Y., Electrophoresis 2003, 24, 2567-2576.
references.citation: Mangelings, D., Maftouh, M., Massart, D. L., Vander Heyden, Y., Electrophoresis 2004, 25, 2808-2816.
references.citation: Desiderio, C., Fanali, S., J. Chromatogr. A 2000, 895, 123-132.
references.citation: Vander Heyden Y., Khots, M. S., Massart, D. L., Anal. Chim. Acta 1993, 276, 189-195.
references.citation: United States Pharmacopeia, 25th Ed., United States Pharmacopeial Convention, Rockville, MD 2001.
references.citation: Vander Heyden, Y., Nijhuis, A., Smeyers-Verbeke, J., Vandeginste, B. G. M., Massart, D. L., J. Pharm. Biomed. Anal. 2001, 24, 723-753.
references.citation: Krull, I. S, Stevenson, R., Mistry, K., Swartz, M. E., Capillary Electrochromatography and Pressurized Flow Capillary Electrochromatography: An Introduction, HNB Publishing, New York 2000.
references.citation: Massart, D. L., Vandeginste, B. G. M., Buydens, L. M. C., De Jong, S., Lewi, P. J., Smeyers-Verbeke, J., Handbook of Chemometrics and Qualimetrics: Part A, Elsevier, Amsterdam 1997.