Aleksandra F. Prokhorova

Chiral analysis of pharmaceuticals by capillary electrophoresis using antibiotics as chiral selectors

The review summarizes the use of the chiral capillary electrophoresis (CE) with different class of antibiotics as chiral selectors in the pharmaceutical field. Basic factors influencing the enantioseparation are shortly discussed. Non-aqueous capillary electrophoresis is also included as well as the coupling of CE to MS. The selection of a chiral selector according the ionic state and structure of the analyte is described. Summary of pharmaceutical applications of chiral CE is given.

Enantiorecognition of profens by capillary electrophoresis using a novel chiral selector eremomycin

The evaluation of a macrocyclic glycopeptide antibiotic, eremomycin, as a chiral selector in capillary electrophoresis (CE) has been performed. The stability of eremomycin in solution and capillary electrolyte, as well as its optical and electrophoretic properties have been discussed. The effect of experimental parameters influencing the enantioseparation of several profens has been studied. Excellent enantioseparation of profens has been achieved and migration order has been validated. Comparison of enantioseparations of profens in CE by using eremomycin-mediated electrolytes and in HPLC with eremomycin immobilized on silica has revealed similar trends for both methods.

Clarithromycin as a chiral selector for enantioseparation of basic compounds in nonaqueous capillary electrophoresis

The first use of macrolide antibiotic clarithromycin (CLM) in nonaqueous media for enantioseparation (partial or baseline) of the following compounds: alprenolol, atenolol, metoprolol, clenbuterol, methoxyphenamine, pindolol, propranolol, sotalol, synephrine, labetalol, and fenoterol is reported. Each analysis took less than 15 min. To find optimal separation conditions, some properties of CLM (adsorption, solubility), as well as the effect of experimental parameters on the enantioseparation of analytes (background electrolyte composition, chiral selector concentration, temperature, and applied voltage) were studied. The best chiral resolution was achieved in methanolic solution of 100 mM citric acid, 10 mM NaOH, 240–300 mM H3BO3, and 60–75 mM CLM. Using the proposed procedure, adsorption of CLM on the capillary wall was negligible and the repeatability of the migration times (RSD) was as good as 1.6%. For the analysis of propranolol, the linearity was achieved in the concentration range 2.5 × 10−2– 3.0 × 10−1 mg/mL with the LODs (3 × S/N) being equal 2.6 × 10−3 mg/mL and 2.8 × 10−3 mg/mL for the first and the second enantiomers, respectively. Linear range for metoprolol enantiomers was 1.0 × 10−2 –1.6 × 10−1 mg/mL. The LODs (3 × S/N) were determined as 2.8 × 10−3 and 3.0 × 10−3 mg/mL for the first and the second enantiomers, respectively.

Enantioseparation of organic acids of pharmaceutical interest using eremomycin as a chiral selector.

Strong adsorption of eremomycin on the fused‐silica capillary wall was used for separation of enantiomers by CE. The capillary with adsorbed chiral selector was shown to be easily prepared and has reproducible properties. The effect of the chiral selector concentration, pH and composition of the BGE, and applied voltage on enantioseparation of acidic compounds, such as profens and aromatic carboxylic acids, was investigated. Two native α‐amino acids, aspartic acid and glutamic acid, were enantioseparated. Fourteen tested compounds (including amino acids) were baseline resolved. Good selectivity of separation (α>1.09) was achieved. The migration order of ibuprofen and ketoprofen enantiomers was determined. The procedures were proposed for the analysis of flurbiprofen and warfarin in pharmaceuticals. Linearity was achieved in the concentration range of 4.0×10−5–2.0×10−3 M for flurbiprofen and 3.2×10−6–4.9×10−6 M for warfarin. The detection limits were found to be about 1×10−5 M for flurbiprofen and 1×10−6 M for warfarin.

Determination of benzoate by paper chromatography with visualization due to its inhibitory activity in the reaction of the photosensitized autooxidation of pyrogallol A

The oxidation of 1,2,4-triacetoxybenzene (Pyrogallol A) and 3,3′,5,5′-tetramethylbenzydine by air oxygen in presence of tris-(2,2′-dipyridyl)ruthenium(II) as a photosensitizer is studied upon irradiation by visible light. The photooxidation of pyrogallol A was inhibited selectively by benzoate at pH 9–11. The rate of the reaction was not affected by other carboxylic acids but was influenced by short-chained aliphatic amines and transition metals. We developed a semiquantitative procedure for the determination of benzoate by paper chromatography. Therein, a common solution of pyrogallol A and a photosensitizer were used for the visualization followed by irradiation with an incandescent bulb. Benzoate was detected as a light spot with Rf ∼ 0.3 against a brown background. The measurement of reflectance intensity for the spot by reflectometry allowed the determination of 1 × 10−5–0.01 M benzoate within a precision of half-order of magnitude. The procedure was validated by comparison to the data of capillary electrophoresis and used to test beverages containing benzoate at levels of 10−4–10−3 M.

Layer-by-Layer Assembly of Polysaccharides and 6,10-Ionene for Separation of Nitrogen-Containing Pharmaceuticals and Their Enantiorecognition by Capillary Electrophoresis

Two silica capillaries modified layer-by-layer with 6,10-ionene and N-(3-sulfo-3-carboxy)-propionylchitosan (SCPC) and with 6,10-ionene and dextran sulfate (DS) were prepared and investigated. Dynamic coating of the capillary efficiently reduces the adsorption of the background electrolyte, sample matrix components, and analytes on its inner wall. Such coatings effect good reproducibility and sensitivity of determination. We demonstrate that separation of betablockers, calcium channel blockers, alpha-adrenergic agonists, H1-blockers, and diuretics was the most efficient and rapid separation with a capillary modified with dextran sulfate. Tetrahydrozoline, carbinoxamine, and furacilin, which are commonly employed as treatments for allergic rhinitis, were identified in human urea. Their concentrations, independently verified by HPLC, were found to be , , and  μg mL−1, with , 0.03, 0.10 μg mL−1, and , 0.8, 0.6 μg mL−1, respectively.

Electrophoretic separation of some nucleosides for the diagnosis of mastopathy and fibroadenoma

Mixtures of 13 normal and modified nucleosides in a 70 mM phosphate buffer solution (pH 6.7) supplemented with 100 mM of sodium dodecyl sulfate were separated by micellar electrokinetic chromatography in 25 min. Electrophoretic profiles of urine are obtained; it is demonstrated that 1-methylinosine and 1-methylguanosine nucleosides can be used as markers of precancerous states (mastopathy) and benign tumors (fibroadenoma).

Electrophoretic enantioseparation of profens in water-methanol solutions using eremomycin as a chiral selector

The possibility of the electrophoretic enantioseparation of profens in water-methanol solution of eremomycin was demonstrated. The effect of the methanol content, phosphate buffer pH, and chiral selector concentration on enantioresolution was studied. Water-methanol background electrolyte was shown to provide better reproducibility of migration times and baseline stability compared to aqueous buffers. The time of analysis in nonaqueous conditions is less than 15 min.

Separation of enantiomers of N -derivatives of amino acids by capillary electrophoresis using macrocyclic antibiotics

The potential for the application of macrocyclic antibiotic eremomycin as a chiral selector for the separation of enantiomers of N-derivatives of amino acids in capillary electrophoresis was estimated. The influence of several factors (the composition and pH of the running electrolyte, the concentration of the chiral selector, capillary geometry, the value of the applied voltage) on the migration of the derivatives of amino acids and enantioselectivity in the presence of eremomycin was studied in order to choose the separation conditions. Using the example of the dansyl derivatives of amino acids the enantioselectivities of vancomycin and eremomycin in capillary electrophoresis were compared.

Chromatographic properties of silica modified with 6,10-ionene and sodium lignosulfonate

Adsorbents for hydrophilic chromatography: silica layer-by-layer modified with 6,10-ionene and sodium lignosulfonate (Sorbent-1), and silica modified with chitosan and sodium lignosulfonate (Sorbent-2) have been investigated. The influence of the nature of polycation used for the synthesis of adsorbents and the composition of the mobile phase on the retention and separation of phenol carboxylic acids have been studied. It was found that the retention of organic acids and the selectivity of their separation are higher on Sorbent-1. The possibility of the isocratic separation of a mixture of caffeine, sorbic, benzoic, vanillic, gallic, salicylic, sinapic, ferulic, p-cumaric, and caffeic acids in 30 min on a column filled with Sorbent-1 was demonstrated.