Enantiomeric Separation of Sibutramine by Capillary Zone Electrophoresis

Abstract

The chiral separation of sibutramine enantiomers was resolved succesfully by capillary zone electrophoresis using cyclodextrins (CDs) as chiral selectors. A complex screening of several different native and derivatized, neutral and ionized cyclodextrine derivatives was performed. The effects of buffer type, concentration and pH, cyclodextrin type and concentration, applied voltage, capillary temperature and injection parameters on the chiral resolution were examined. The best results on a very short fused silica capillary of 30 cm × 50 μm were obtained using a 50 mmol L −1 phosphate buffer containing 10 mmol L −1 randomly methylated β-CD at a pH of 4.5, 15 kV of voltage, temperature of 15 °C, injection parameters of 30 mbar s −1 and ultraviolet (UV) detection at 220 nm. The analytical performances of the optimized method were verified in terms of linearity, precision and robustness, and limit of detection and quantification were calculated.

Analytical Methodologies for the Stereoselective Determination of Sibutramine: An Overview

“…Capillary zone electrophoresis (CZE) using derivatized neutral CD -methyl-β-CD (M-β-CD) or derivatized ionized CD -carboxymethyl-β-CD as chiral (CM-β-CD) selectors was the first-choice method used in several studies for the enantioseparation of SIB enantiomers [27][28][29][30].…”

“…During the optimization process, the effects of buffer composition, background electrolyte concentration and pH, CD type and concentration, applied voltage, capillary temperature and injection parameters on the chiral resolution were studied. The best results on a short fused silica capillary of 30 cm × 50 µm were obtained using a 50 mM phosphate buffer containing 10 mM randomly methylated β-CD (RAMEB) as chiral selector at a pH of 4.50 with UV detection at 220 nm; the separation of enantiomers was achieved in approximately 5 minutes [29].…”

Interpol review of controlled substances 2016–2019

“…Sibutramine: 2016 spectrofluorometric method for analysis of sibutramine, indapamide and hydrochlorothiazide compounds in weight-reducing tonic samples [ 442 ]; enantiomeric separation of Sibutramine by capillary zone electrophoresis using cyclodextrins as chiral selectors [ 443 ]; determination of Sibutramine in slimming food supplements by a validated HPLC-ES-MS/MS method [ 444 ]; thermal behaviors of racemic sibutramine hydrochloride monohydrate as well as that of the anhydrous state were investigated by differential scanning calorimetry (DSC) [ 445 ]; a ‘natural’ weight loss product containing sibutramine [ 446 ]; simultaneous detection of sibutramine and phenolphthalein by CE [ 447 ]; 2017 ATR-FTIR spectroscopic method to detect sibutramine in dietetic herbal foods, teas and dietary supplements [ 448 ]; identification of sibutramine using a fully integrated GC/FT-IR/MS instrument [ 449 ]; SERS method for detection of Sibutramine HCL in seven types of commercial slimming capsules [ 450 ]; 2018 continuation of Lanzarotta’s 2017 study using fully integrated GC-FT-IR-MS to identify and confirm the presence of sibutramine and AB-FUBINACA [ 451 ]; HPLC-PDA, LC-Q-TOF/MS, FT-IR, and NMR for isolation and structural characterization of a novel sibutramine analogue, chlorosipentramine, in a slimming dietary supplement [ 452 ]; LC-MS/MS (ESI) method for detecting sibutramine in herbal supplements [ 453 ]; 2019 identification of slimming agents apprehended in Brazil using FTIR, Differential Scanning Calorimetry and GC-MS including the comparison of the efficiency of solid-liquid extraction and microwave-assisted extraction [ 454 ]; portable square-wave voltammetric method for fast screening and quantification of sibutramine in herbal formulations and dietary supplements samples [ 455 ].…”

Chiral selectors in CE: Recent development and applications (mid‐2014 to mid‐2016)

“…Moreover, when M‐β‐CD was used as a CS, the complexation constants were higher for 10‐hydroxywarfarin than for warfarin, and therefore, the former exerts stronger affinity to M‐β‐CD and stronger stereoselective effect. RAMEB was used in CE as a CS for the enantioseparation of several analytes, such as omeprazole, amlodipine, and ofloxacin . Briefly, Hancu et al.…”

“…Among all the examined CDs, RAMEB was selected as the optimum since it provided the best R S (2.48) at the shortest analysis time (<6 min). RAMEB was also used for the chiral separation of sibutramine, and the method was validated based on linearity, precision, LOD, LOQ, and intra‐ and interday reproducibility . In a recent study , molecular modeling demonstrated that RAMEB interacts with ofloxacin enantiomers mainly by Van der Waals forces, and a small difference in the binding energies of the two enantiomers was observed.…”