Chlorpheniramine maleate enantioseparación using carbon nanotubes and cyclodextrins as chiral selectors by fia with fluorescent detection.

ACOSTA, GIMENA; SILVA, RAUL; GOMEZ, ROXANA A.; FERNANDEZ, LILIANA

Santa Fe

Congreso; II Reunión Internacional de Ciencias Farmacéuticas; 2012

CHLORPHENIRAMINE MALEATE ENANTIOSEPARATION USING CARBON NANOTUBES AND CYCLODEXTRINS AS CHIRAL SELECTORS BY FIA WITH FLUORESCENT DETECTION Acosta MG, Silva RA, Gil RA, Gómez MR, Fernández LP# Área de Química Analítica, INQUISAL-CONICET, Facultad de Química, Bioquímica y Farmacia, Universidad Nacional de San Luis, Chacabuco 917, San Luis, CP: 5700 Introduction Many drugs used in therapeutics have a chiral center and in most cases the pharmacological activity is restricted to one of the enantiomers; whereas the remaining form show no effect or produce different therapeutic. Chlorpheniramine maleate (CPA) is used in the treatment of allergic, to relieve rhinitis, sneezing, itchy eyes, nose and throat. The International Conference on Harmonization (ICH) establish, for the quality control of chiral drugs marketed as single enantiomer, that the undesired enantiomer must be considered as any other impurity (1). Hence, the development of methods for enantioselective analysis which enable monitoring of the enantiomeric purity becomes very important tools for drug quality control. The multiwalled carbon nanotubes (MWCNTs) have been applied for the development of higher performance separation techniques that utilize nanoscale interactions (2). Moreover, considering their chiral structure, MWCNTs have been applied in order to achieve enantioseparation of pharmaceutical compounds. On the other hand, the use of cyclodextrins (CDs) as chiral selectors is the most frequently approach applied in the enantiomer separations. A multicriterium optimization was applied to find the best conditions that met the analytical requirements (3). The aim of this work was to develop a methodology of flow injection-solid phase extraction (FI-SPE) with fluorescence detection for the enantioseparation of (±)-CPA using MWCNTs and β-CD. Materials and methods All experiments were carried out on a Shimadzu RF-5301PC spectrofluorimeter (Shimadzu Corporation), equipped with a high-intensity Xenon discharge lamp. A model-5020 six-port two-way rotary valve from Rheodhyne was used to set up the FIA manifold. Two Minipuls 3 peristaltic pumps from Gilson with 1.3-mm ID Tygon pumping tubing to propel the reagents and samples were used. (±)-CPA, β-CD, and MWCNTs were purchased from Sigma, Sodium dodecylsulphate (SDS) was purchased from Tokyo Kasei Industries. All other reagents and solvents were of analytical grade. Mixtures of SDS-HCl, in different relations were evaluated as eluents. A 10.0 mg of MWCNTs conical microcolumn was employed to achieve the enantioseparation of CPA. Experimental design was performed by using the software Stat-Ease Design-Expert trial Version 8.0. Results (±)-CPA solution 1mM was disolved in doubly distilled water. The different -CD:(±)-CPA relations were obtained by suitably diluting the both standard solutions in water. Solutions were into microcolumn at different inject rates (5-20 rpm). The eluent solutions (SDS 0,02M:HCl 0,01M) were studied in several relations (10:90; 20:80; 30:70 and 40:60). The (±)-CPA enantioseparation was monitored at 367 nm (λext = 240 nm). An adequate enantioresolution (2.01) was achieved applying the proposed methodology under optimized conditions: -CD = 2.08 mM; HCl concentration = 5.00 x 10-3 M; SDS concentration = 1.00 x 10-3 M and eluent flow rate = 15.00 rpm. Conclusions The present methodology joins the chiral properties of MWCNTs and -CD to achieve enantioseparation of chiral drugs, involving a continuous non-chromatographic separation process coupled to spectroflurimetry detection that enabled high sample throughput and low sample and reagents consumption making it suitable for drug quality control. Also the experimental variables that influence on resolution and sensitivity were optimized by the application of a multivariate design approach. #Corresponding author. Tel +54 266 4425385, fax +54 266 4430224; e-mail: lfernand@unsl.edu.ar References 1) CPMP/ICH/367/96: ICH topic Q6A: Specifications: Test procedures and acceptance criteria for new drug substances and new drug products: chemical substances. ICH. Geneva, Switzerland. 2) Herrera-Herrera AV, González-Curbelo MA, Hernández-Borges J, Rodríguez-Delgado MA. Carbon nanotubes applications in separation science: A review. Anal. Chim. Acta. 2012; http://dx.doi.org/10.1016/j.aca.2012.04.035. 3) L. Vera-Candioti, A.Olivieri, H.Goicoechea. Simultaneous multiresponse optimization applied to epinastine determination in human serum by using capillary electrophoresis. Anal Chim. Acta. 2007; 595: 310?318.