Enantioselective determination of thyroxine enantiomers by ligand‐exchange CE with UV absorbance and ICP‐MS detection

Abstract

A simple CE method has been developed for the separation and determination of thyroxine (T 4 ) enantiomers in pharmaceutical formulations. The method was based on ligand-exchange mechanism using a Cu(II)/L-proline complex as chiral selector. The effects of different parameters affecting separation such as chiral selector concentration, organic additive, buffer pH and temperature were investigated. A baseline separation of the two enantiomers was obtained at a Cu(II)/L-proline ratio of 1:8 in a borate buffer (15 mmol/L, pH 9.6) containing 10% v/v acetonitrile. Under the optimized conditions, precision linearity range and detection limits of the developed enantioselective CE method were evaluated and compared using two different detection systems: conventional UV detection at 226 nm and iodine ( 127 I)specific detection (''chiral speciation'') with ICP-MS. Both methodologies show adequate analytical performance characteristics with detection limits around 0.30 mg/mL for each enantiomer of T 4 . Finally, a levothroid pharmaceutical formulation sample was successfully analyzed using both developed methods CE-UV and CE-ICP-MS.

Enantioseparation of tartaric acid by ligand‐exchange capillary electrophoresis using contactless conductivity detection

“…The influence of temperature on the separation was studied, and a temperature >25°C (ambient laboratory temperature) led to faster migration times of d,l ‐tartaric acid and hence lower resolution. Similar results were observed in another LE‐CE separation of thyroxine enantiomers . Lower temperatures were not studied because the BGE vials could not be cooled under the ambient temperature and thermostatting of only the capillary cassette is not sufficient to provide a lower temperature in the whole separation system.…”

“…Separation based on a ligand‐exchange (LE) mechanism in CE is another commonly used approach for the separation of enantiomers based on enantioselective complexation between the enantiomers and a metal–ligand complex forming a metastable ternary diastereomer. As metal ions, copper(II) is the most frequently used, followed by zinc(II) and nickel(II) . Therefore, this technique can only be used for analytes that have complex‐formation properties (e.g.…”

Chiral separation using capillary electromigration techniques based on ligand exchange principle

“…González et al. used this complex as chiral selector for the separation and determination of thyroxine enantiomers in pharmaceutical formulations with UV absorbance and inductively coupled plasma‐mass spectrometry (ICP‐MS) detection []. Interestingly, because of the addition of acetonitrile to the running buffer, a baseline separation of thyroxine enantiomers was obtained at a Cu(II)‐L‐proline ratio of 1:8, which is quite different from the optimum ratio of 1:2 reported by other literatures (Fig.…”

Chiral electromigration techniques in pharmaceutical and biomedical analysis

“…The application of CE in drug impurity analysis has been summarized [79,80]. Table 1 clearly reflects the general trend that CDs are by far the most widely used chiral selectors although some studies utilized other additives such as BSA [81], maltodextrin [82], (+)-18C6H4 [83], ligand exchange [84] or the chiral ionic liquid ethylcholine bis(trifluoromethylsulfonyl) Baclofen α-CD (18 mM) 0.1 M sodium borate, pH 9.9, 1% acetonitrile 2-10 μg/ml, analysis of racemic bulk drug and tablets [103] Benzimidazole derivatives Chloroquine SBE-β-CD (30 mg/ml) 100 mM sodium phosphate, pH 2.5 0.02%, analysis of laboratory sample [108] Clopidogrel Sulfated β-CD (5%) 10 mM triethylamine/phosphoric acid 0.08-0.33 μg/ml, minor enantiomer and related substances [109] Dexamphetamine HDAS-β-CD (10 mg/ml) 0.1 M sodium phosphate buffer, pH 2.5 0.06%, minor enantiomer and charged related substances [91] Dexamphetamine Sulfated β-CD (25 mg/ml), SBE-β-CD (80 mg/ml) 50 mM sodium phosphate buffer, pH 2.5 0.01-0.02%, minor enantiomer and related substances [92] Dexamphetamine Sulfated β-CD (5.5%) 1.5% SDS, 0.5% ethyl acetate, 3.5% 1-butanol, 2.5% 2-propanol and 92% 50 mM sodium phosphate buffer, pH 3.0 0.05-0.2%, minor enantiomer and related substances [93] Econazole HP-γ-CD (40 mM) 50 mM SDS in 20 mM phosphate buffer, pH 8.0…”