Abstract
Tramadol is a centrally acting analgesic drug, used in therapy as a racemic mixture of its trans enantiomers: (1R,2R) and (1S,2S). A simple capillary electrophoresis (CE) method was developed for the chiral separation of tramadol enantiomers using carboxymethyl-β-CD (CM- β-CD) as chiral selector. Influence of buffer pH and concentration, CD concentration, capillary temperature, applied voltage and injection parameters on the chiral separation was evaluated. Optimization of the analytical conditions was performed using a preliminary “one factor at time” approach followed by a faced-centred central composite design. The best results were obtained when using 25 mM sodium tetraborate buffer at pH 11.0, 5 mM CM-β-CD as chiral selector, + 17.5 kV voltage, 15 °C temperature, and 30 mbar/1 s hydrodynamic injection. The analytical performance of the method was evaluated in terms of precision, linearity, accuracy, detectability and robustness. The method was applied successfully for the determination of tramadol enantiomers from pharmaceutical formulations.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Bezerra MA, Santelli RE, Oliveira EP, Villar LS, Escaleira LA (2008) Response surface methodology (RSM) as a tool for optimization in analytical chemistry. Talanta 76:965–977. https://doi.org/10.1016/j.talanta.2008.05.019
Candioti LV, De Zan MM, Camara MS, Goichoechea HC (2014) Experimental design and multiple response optimization. Using the desirability function in analytical methods development. Talanta 124:123–138. https://doi.org/10.1016/j.talanta.2014.01.034
Chalavi S, Fakhari AR, Nojavan S, Mirzaei P (2018) Evaluation of the synergistic effect with amino acids for enantioseparation of basic drugs using capillary electrophoresis. Electrophoresis 39:2022–2029. https://doi.org/10.1002/elps.201800128
Chan ECY, Ho PC (1998) Enantiomeric separation of tramadol hydrochloride and its metabolites by cyclodextrin-mediated capillary zone electrophoresis. J Chromatogr B 707:287–294. https://doi.org/10.1016/S0378-4347(97)00605-1
Chankvetadze B (2018) Contemporary theory of enantioseparations in capillary electrophoresis. J Chromatogr A 1567:2–25. https://doi.org/10.1016/j.chroma.2018.07.041
Fang L, Du Y, Hu X, Luo L, Guo X, Yu J (2017) Carboxymethyl β-cyclodextrin as chiral selector in capillary electrophoresis: enantioseparation of 16 basic chiral drugs and its chiral recognition mechanism associated with drugs' structural features. Biomed Chromatogr 31:e3991. https://doi.org/10.1002/bmc.3991
Fukuda IM, Pinto CFF, Moreira CS, Saviano AM, Lourenco FR (2018) Design of experiments (DoE) applied to pharmaceutical and analytical quality by design (QbD). Braz J Pharm Sci 54:e01006. https://doi.org/10.1590/s2175-97902018000001006
Grond S, Sablotzki A (2004) Clinical pharmacology of tramadol. Clin Pharmacokinet 43:879–923. https://doi.org/10.2165/00003088-200443130-00004
Miotto K, Cho AK, Khalil MA, Blanco K, Sasaki JD, Rawson R (2017) Trends in tramadol: pharmacology, metabolism and misuse. Anesth Analg 124:44–51. https://doi.org/10.1213/ANE.0000000000001683
Mohammadi A, Nojavan S, Rouini M, Fakhari AR (2011) Stability evaluation of tramadol enantiomers using a chiral stability-indicating capillary electrophoresis method and its application to pharmaceutical analysis. J Sep Sci 34:1613–1620. https://doi.org/10.1002/jssc.201100021
Naghdi E, Fakhari AR (2018) Simultaneous chiral separation of tramadol and methadone in tablets, human urine, and plasma by capillary electrophoresis using maltodextrin as chiral selector. Chirality 30:1161–1168. https://doi.org/10.1002/chir.23008
Parr MK, Schmidt AH (2018) Life cycle management of analytical methods. J Pharm Biomed Anal 147:506–517. https://doi.org/10.1016/j.jpba.2017.06.020
Rezanska P, Navratilova K, Rezanska M, Kral V, Sykora D (2014) Application of cyclodextrins in chiral capillary electrophoresis. Electrophoresis 35:2701–2721. https://doi.org/10.1002/elps.201400145
Rudaz S, Veuthey JL, Desiderio C, Fanali S (1998) Use of cyclodextrins: resolution of tramadol enantiomers. Electrophoresis 19:2883–2889. https://doi.org/10.1002/elps.1150191614
Rudaz S, Veuthey JL, Desiderio C, Fanali S (1999) Simultaneous stereoselective analysis by capillary electrophoresis of tramadol enantiomers and their main phase I metabolites in urine. J Chromatogr A 846:227–237. https://doi.org/10.1016/S0021-9673(99)00028-X
Rudaz S, Cherkaoui S, Dayer P, Fanali S, Veuthey JL (2000) Simultaneous stereoselective analysis of tramadol and its main phase I metabolites by on-line capillary zone electrophoresis–electrospray ionization mass spectrometry. J Chromatogr A 868:295–303. https://doi.org/10.1016/S0021-9673(99)01257-1
Rudaz S, Le Saux T, Prat J, Gareil P, Veuthey JL (2004) Ultrashort partial-filling technique in capillary electrophoresis for infinite resolution of tramadol enantiomers and its metabolites with highly sulfated cyclodextrins. Electrophoresis 25:2761–2771. https://doi.org/10.1002/elps.200406052
Scott LJ, Perry CM (2000) Tramadol: a review of its use in perioperative pain. Drugs 60:139–176. https://doi.org/10.2165/00003495-200060010-00008
Shipton EA (2000) Tramadol-present and future. Anaesth Intensive Care 28:363–374
Soetebeer UB, Schierenberg MO, Schulz H, Andresen P, Blaschke G (2001) Direct chiral assay of tramadol and detection of the phase II metabolite O-demethyl tramadol glucuronide in human urine using capillary electrophoresis with laser-induced native fluorescence detection. J Chromatogr B 765:3–13. https://doi.org/10.1016/S0378-4347(01)00366-8
Tabani H, Mahyari M, Sahragard A, Fakhari AR, Shaabani A (2015) Evaluation of sulfated maltodextrin as a novel anionic chiral selector for the enantioseparation of basic chiral drugs by capillary electrophoresis. Electrophoresis 36:305–311. https://doi.org/10.1002/elps.201400370
Zandkarimi M, Shafaati A, Foroutan SM, Oliaee NH, Eslamparast A (2005) Separation of tramadol enantiomers by capillary electrophoresis using highly sulfated cyclodextrins. DARU 13:143–147
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
On behalf of all authors, the corresponding author states that there is no conflict of interest.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Sarkany, A., Hancu, G., Cârje, A. et al. Chiral separation of tramadol enantiomers by capillary electrophoresis using cyclodextrins as chiral selectors and experimental design method optimization. Chem. Pap. 73, 2363–2370 (2019). https://doi.org/10.1007/s11696-019-00789-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11696-019-00789-8