Recent developments in the methodology and application of MEEKC

MEEKC is an electrodriven separation technique that utilises the unique properties of a microemulsion (ME) as a background electrolyte to achieve separation of a diverse range of solutes. MEs are composed of nanometre-sized oil droplets suspended in aqueous buffer, which is commonly referred to as oil-in-water ME. The droplets are stabilised by the presence of both a surfactant and co-surfactant. The use of water-in-oil MEs in MEEKC has also been investigated. This review details the advances in MEEKC-based separations from the period June 2008 - June 2010. Areas covered include online sample concentration, suppressed electroosmosis MEEKC, chiral separations, MEEKC-MS, MEEKC-ICP-MS and ME structure characterisation. The review also includes a fundamental introduction to MEEKC, along with a review of recent applications.     

An overview of the applications of capillary electrophoresis to the analysis of pharmaceutical raw materials and excipients

Summary The use of capillary electrophoresis for the separation and quantitation of a range of pharmaceutical raw materials and excipients is reviewed. Capillary electrophoresis is shown to be a useful and versatile technique for a large number of applications. Features of the various methods include simplicity, detection of poor chromatophore species by extensive use of indirect UV detection or direct absorbance at low wavelengths, minimal operating costs and generation of high quality retrievable raw data. Specific novel examples described include separations of lactose, flavouring agents, inorganic salts, lecithin constituents, a range of organic acids, benzylalkonium chloride components, sodium lauryl sulphate, and the quality of input water. It is concluded that the versatility of CE will ensure that it is increasingly used in the analysis of pharmaceutical raw materials and excipients.     

High voltage capillary zone electrophoresis: Operating parameters effects on electroendosmotic flows and electrophoretic mobilities

Summary In High Voltage Capillary Zone Electrophoresis a field is applied across a narrow bore capillary filled with electrolyte solution. An electroendosmotic (EEO) flow is generated within this capillary which sweeps solutes along the tube. An absolute method of flow estimation is described, along with some operating parameter effects on the solute mobility. System parameters enabling flow direction reversal and a zero flow are described. The use of several capillaries simultaneously and the effect of pH on EEO flow rates are also shown. Effects of various operating parameters on solute resolution are also detailed.     

Selective and quantitative analysis of 4-hydroxybenzoate preservatives by microemulsion electrokinetic chromatography

A microemulsion electrokinetic chromatography (MEEKC) method has been developed and validated for the determination of 4-hydroxybenzoates and their impurities. These materials are commonly known as parabens and are widely used as preservatives in foods, cosmetics and pharmaceuticals. The method was shown to be selective and quantitative for the methyl, ethyl, propyl and butyl esters of 4-hydroxybenzoic acid. An internal standard, 4-hydroxyacetophenone, was employed to improve injection precision and detector linearity. In addition, 4-hydroxybenzoic acid, the major degradent, could also be monitored at the 0.1% (m/m) level. The method was successfully validated for assay and detection of the impurities in 4-hydroxybenzoic acid methyl ester and 4-hydroxybenzoic acid propyl ester samples and for the determination of 4-hydroxybenzoic acid methyl ester in a liquid pharmaceutical formulation. The determination of paraben content by MEEKC in a liquid sample was consistent with HPLC analysis. This work is the first reported validated MEEKC method and shows that the methodology can be successfully implemented into routine quality control testing.     

Background and operating parameters in microemulsion electrokinetic chromatography

Microemulsion electrokinetic chromatography (MEEKC) is an electrodriven separation technique. Separations are generally achieved using microemulsions consisting of surfactant-coated nanometer-sized oil droplets suspended in aqueous buffer. A cosurfactant such as a short-chain alcohol is generally used to stabilize the microemulsion. This review summarizes the various microemulsion types and compositions that have been used in MEEKC. The effects of key-operating variables such as surfactant type and concentration, cosurfactant type and concentration, buffer pH and type, oil type and concentration, use of organic solvent and cyclodextrin additions, and temperature are described. Specific examples of water-in-oil microemulsions and chirally selective separations are also covered.     

Predicting electrophoretic mobility of beta-blockers in a water-methanol based electrolyte system

Summary Applicability of a mathematical model to predict the electrophoretic mobility of structurally related analyses is shown using generated mobility data for beta-blockers in a mixed aqueousmethanolic buffer. The mobilities of atenolol, alprenolol, labetalol and metoprolol in binary mixed solvent buffers containing different concentrations of methanol have been employed to train the model. Then the mobilities of propranolol, timolol and acebutalol have been predicted using the trained model. The produced mean prediction errors employing two and one experimental data points for three beta-blockers are 1.6 and 2.8%, respectively, which is easily within experimental uncertainty.     

Preliminary Study on the Use of Water-in-Oil Microemulsion Eluents in HPLC

This paper describes the use of water-in-oil (W/O) microemulsion eluents to achieve unique normal phase HPLC separations. The effects of varying the oil type, co-surfactant, surfactant, use of mixed surfactant and water concentration upon the chromatographic performance was assessed. Other parameters such as temperature and flow rate were also investigated. An optimised set of W/O microemulsion HPLC (MELC) operating conditions was then applied to the separation of a range of acids, bases and neutral compounds. The more water soluble compounds were more highly retained. W/O MELC was found to be especially suitable for determination of water insoluble compounds. The drug content in bumetanide tablets was determined by W/O MELC with good linearity and accuracy. The solubilising ability of the W/O microemulsion reduced sample preparation (precipitation and extraction) requirements compared to conventional HPLC. The results obtained compared well with those obtained by a validated reverse phase HPLC method. It is recommended that W/O MELC should be considered for routine applications, especially for the analysis of water insoluble compounds in complex sample matrices. Further research is recommended to more definitely assess the operating parameters of W/O MELC and to determine other applications.     

Oil-in-Water Microemulsion High Performance Liquid Chromatographic Analysis of Pharmaceuticals

Efficient and novel oil-in-water microemulsion HPLC separations of a range of solutes have been achieved using isocratic elution and a conventional reversed-phase HPLC column. A single set of isocratic oil-in-water microemulsion HPLC conditions are shown to be successful for the resolution of a wide range of basic, neutral and acidic drugs and excipients. A robust separation method was developed for the quantitative analysis of Naproxen in a tablet formulation. The method offered a similar run time and improved chromatography when compared to conventional HPLC modes, demonstrating its potential for routine use. In developing the separations the effect on the chromatography of varying the operating parameters was studied. While generally the method was robust to changes in some variables, others markedly changed the separation selectivity, solute retention, peak-peak resolution or resulted in poor chromatographic performance. The method was found to be compatible with very low UV working detection wavelengths. As a final stage to the experimental programme, a microemulsion method was developed with the capability of analysing a range of water-insoluble drugs.