Analytical Methodologies for the Stereoselective Determination of Sibutramine: An Overview

Open access


Sibutramine is a chiral anti-obesity drug which decreases food intake and increases energy expenditure. In therapy it is used as a racemic mixture; however both pharmacokinetic and pharmacodynamic data have revealed enantioselective behavior of sibutramine and its major active metabolites. Several chromatographic and electrophoretic analytical methods have been published so far for the chiral determination of sibutramine from pharmaceutical preparations and biological samples. The current paper aims to provide a systematic review of the stereochemical aspects and analytical methods used for the enantiodetermination of sibutramine and its active enantiomers covering the last 15 years.

If the inline PDF is not rendering correctly, you can download the PDF file here.

  • 1. Luque CA Rey JA - The discovery and status of sibutramine as an antiobesity drug. Eur J Pharmacol. 2002;(2-3):119-128.

  • 2. Finer N. - Sibutramine: its mode of action and efficacy. Int J Obes Relat Metab Disord. 2002;26(4):29-33.

  • 3. Nisoli E Carruba MO - An assessment of the safety and efficacy of sibutramine an anti-obesity drug with a novel mechanism of action. Obes Rev. 2000;1(2):127-139.

  • 4. Bodhankar SL Thakurdesai PA Singhal S et al. - Anorexic effect of (R)-sibutramine: comparison with (RS)-sibutramine and (S)-sibutramine. Indian J Physiol Pharmacol. 2007;51(2):175-178.

  • 5. Filippatos TD Kiortsis DN Liberopoulos EN et al. - A review of the metabolic effects of sibutramine. Curr Med Res Opin. 2005;21(3):457-468.

  • 6. Glick SD Haskew RE Maisonneuve IM et al. - Enantioselective behavioral effects of sibutramine metabolites. Eur J Pharmacol. 2000;397:93-102.

  • 7. Noh K Bae K Min B et al. - Enantioselective pharmacokinetics of sibutramine in rat. Arch Pharm Res. 2010;33:267-273.

  • 8. Tyczynski JE Oleske DM Klingman D et al. - Safety assessment of an anti-obesity drug (sibutramine): a retrospective cohort study. Drug Saf. 2012;35(8):629-644.

  • 9. Maggioni AP Caterson ID Urso R et al. - Relation between weight loss and causes of death in patients with cardiovascular disease: finding from the SCOUT trial. J Cardiovasc Med. 2017;18(3):144-151.

  • 10. Scheen AJ - Cardiovascular risk-benefit profile of sibutramine. Am J Cardiovasc Drugs. 2010; 10(5):321-334.

  • 11. Dunn JD Gryniewicz-Ruzicka CM Kauffman JF et al.- Using a portable ion mobility spectrometer to screen dietary supplements for sibutramine. J Pharm Biomed Anal. 2011; 54(3):469-474.

  • 12. Diefenbach IC Friedrich M Dos Santos MR et al. - Development and validation of a column high-performance liquid chromatographic method for determination of sibutramine in capsules. J AOAC Int. 2009; 92(1):148-151.

  • 13. Rebiere H Guinot P Civade C et al. - Detection of hazardous weightloss substances in adulterated slimming formulations using ultra-highpressure liquid chromatography with diode-array detection. Food Addit Contam Part A Chem Anal Control Expo Risk Assess. 2012;29(2):161-171.

  • 14. Um SY Kim KB Kim SH et al. - Determination of the active metabolites of sibutramine in rat serum using column-switching HPLC. J Sep Sci. 2008;31(15):2820-2826.

  • 15. Bae JW Choi CI Jang CG et al. - Simultaneous determination of sibutramine and its active metabolites in human plasma by LC-MS/MS and its application to a pharmacokinetic study. Biomed Chromatogr. 2011;25(11):1181-1188.

  • 16. Fang QK Senanayake CH Han Z et al. - First preparation of enantiomerically pure sibutramine and its major metabolite and determination of their absolute configuration by single crystal X-ray analysis. Tetrahedron Asymmetry 1999; 10:4477-4480.

  • 17. Han Z Krishnamurthy D Pflum D et al. - First practical synthesis of enantiomerically pure (R)- and (S)-desmethylsibutramine (DMS) and unambiguous determination of their absolute configuration by singlecrystal X-ray analysis. Tetrahedron Asymmetry 2002;13(2):107-109.

  • 18. Krishnamurthy D Han Z Wald SA et al. - First asymmetric synthesis of (R)-desmethylsibutramine. Tetrahedron Asymmetry 2002;43(13):2331-2333.

  • 19. Han Z Krishnamurthy D Fang QF et al. - New resolution approach for large-scale preparation of enantiopure didesmethylsibutramine (DDMS). Tetrahedron Asymmetry 2003;14(22):3533-3536.

  • 20. Bojarski J Aboun-Enein HY Ghanem A - What’s new in chromatographic enantioseparations. Curr Anal Chem. 2005;1:59-97.

  • 21. Singh AK Pedro LG Gomes FP et al. - Development and validation of sensitive methods for determination of sibutramine hydrochloride monohydrate and direct enantiomeric separation on a protein-based chiral stationary phase. J. AOAC Int. 2008; 91(3):572-579.

  • 22. Radhakrishna T Lakshmi-Narayana C Sreenivas-Rao D et al. - LC method for the determination of assay and purity of sibutramine hydrochloride and its enantiomers by chiral chromatography. J Pharm Biomed Anal. 2000;22:627-639.

  • 23. Bae K Noh K Jang K et al. - Analysis of enantiomers of sibutramine and its metabolites in rat plasma by liquid chromatography-mass spectrometry using a chiral stationary-phase column. J Pharm Biomed Anal. 2009;50(2):267-70.

  • 24. Kang W Bae K Noh K - Enantioselective determination of sibutramine and its active metabolites in human plasma. J Pharm Biomed Anal. 2009; 51:264-267.

  • 25. Scriba GK - Differentiation of enantiomers by capillary electrophoresis. Top Curr Chem. 2013; 340:209-275.

  • 26. Rezanka P Navrátilová K Rezanka M et al. - Application of cyclodextrins in chiral capillary electrophoresis. Electrophoresis. 2014; 35(19):2701-2721.

  • 27. Zhu H Wu E Chen J et al. - Enantioseparation and determination of sibutramine in pharmaceutical formulations by capillary electrophoresis. Bull. Korean Chem. Soc. 2010; 31:1496-1500.

  • 28. Lee YJ Choi S Lee J et al. - Chiral discrimination of sibutramine enantiomers by capillary electrophoresis and proton nuclear magnetic resonance spectroscopy. Arch Pharm Sci Res. 2012;35(4):671-681.

  • 29. Hancu G Hilochie A Vlad RA et al. - Enantiomeric separation of sibutramine by capillary zone electrophoresis. J Braz Chem Soc. 2016;27(6):1116-1120.

  • 30. Zhu H Wu E Chen J et al. - Reverse migration order of sibutramine enantiomers as a function of cyclodextrin concentration in capillary electrophoresis. J Pharm Biomed Anal. 2011; 54:1007-1112.

  • 31. Fang L Yu J Jiang Z et al. - Preparation of a β-cyclodextrin-based open-tubular capillary electrochromatography column and application for enantioseparations of ten basic drugs. PLoS One. 2016; 15(1): e0146292.

Journal information
All Time Past Year Past 30 Days
Abstract Views 0 0 0
Full Text Views 207 126 11
PDF Downloads 115 82 21