Details

Autor(en) / Beteiligte

• Mahuzier, P-E

Titel

Studies into the optimisation and application of microemulsion electrokinetic chromatography for pharmaceutical analysis

Ort / Verlag

ProQuest Dissertations & Theses

Erscheinungsjahr

2003

Quelle

ProQuest Dissertations & Theses A&I

Beschreibungen/Notizen

• Microemulsion electrokinetic capillary chromatography (MEEKC) is similar to micellar electrokinetic chromatography in that it separates neutral solutes based on their chromatographic retention factors. Separations are achieved using microemulsion, which are nanometre size oil droplets suspended in aqueous buffer. The surface tension between the oil and water components is reduced by covering the oil droplet with an anionic surfactant such as SDS and a co-surfactant such as a short chain alcohol. In MEEKC solutes partition between the aqueous phase and oil droplets, which are moving through the solution. In this research programme, microemulsion electrokinetic chromatography in CE is studied in depths to include novel approaches to method development and optimisation. These include an evaluation of selectivity changes by using a test-mixture containing nine solutes. The test-mixture included insoluble and soluble acids, bases and neutrals. The selectivity of microemulsions for the test-mixture has been studied by examining a large number of factors to include organic solvents, co-surfactants, urea, temperature, cyclodextrins and ion-pair reagents. Previous reports on the selectivity in MEEKC have concentrated only on neutral solutes and in this work a range of analytes is examined. The separation selectivity was considerably changed with the addition of an alcohol such as butan-1-ol, propan-2-ol, cyclodextrins or using a low pH buffer. Cyclodextrins are investigated in detail with specific test-mixtures. The separation selectivity was largely unaffected by the use of methanol or acetonitrile, surfactant concentration, buffer type, oil type, sample diluents or type of the counter-ion or filtration. Migration times were dramatically altered with the use of ion-pair reagent and buffer concentration. It was also demonstrated that temperature variations alter the migration time but not the selectivity. An application of MEEKC in CE, which was studied in detail, was the development and validation of a method for the determination of the drug content of commercial Naproxen tablets. In this investigation degradation, accuracy, linearity and repeatability studies were performed. With the same buffer, another direct application was the determination of Rizatriptan in a pharmaceutical preparation. These methods are now routinely used in GlaxoSmithKline. A capillary electrophoresis method has also been developed and validated for the assay 4-hydroxybenzoates (parabens) and their impurities. These compound are widely used as preservatives in both food and pharmaceutical drugs. To complete this study the MEEKC buffer was slightly modified to obtain the best selective and a quantitative method for methyl, ethyl, propyl and butyl paraben. Hydroxybenzoic acid, the major degradent of the paraben, can also be monitored with this method. An internal standard was employed to improve injection precision and detector linearity in the assays. The method was then validated for assay of impurities in methyl paraben and propyl paraben samples.