Comparison of liquid chromatography and capillary electrophoresis methods for quantification of sodium residuals.

Liquid chromatography (LC) and capillary electrophoresis (CE) methods were developed to perform the determination of residual sodium in mother liquors and successive washes of an active pharmaceutical ingredient (API). The addition of sodium chloride to the product solution results in rapid and complete crystallization of the API. The LC method was coupled to evaporative light scattering detection (ELSD) while the CE approach was based on indirect UV detection. Both methods were fully validated. Selectivity, response function, trueness, precision, accuracy, linearity and limits of detection (LOD) and quantification (LOQ) were the criteria investigated. The LC-ELSD method was found to be more sensitive than the CE/indirect UV approach. The methods were found to be valid over concentration ranges of 62-500 and 235-1500 ppm for the LC and the CE methods, respectively. Both methods were compared and used for the determination of actual samples coming from different batches of the same API chemical synthesis.

Determination of pK(a) values of basic new drug substances by CE.

During the discovery phase for chemical entities as potential new drugs, the determination of pK(a) values can be a very valuable parameter in the selection process. In general, at the very beginning, only small amounts of these active pharmaceutical ingredients (API) are available for analytical characterisation. One drawback of traditional methods such as titration and UV spectroscopy is that they require large amounts of high purity material. As an alternative technique, a method by capillary electrophoresis (CE) which is based on migration times or mobilities of the ionic species over a range of pH values has been evaluated for the determination of pK(a). From the relationship between measured mobilities and pH of electrolyte, a S-shaped curve was obtained and pK(a) values determined for some new API entering the screening phase. On the basis of our experience, the pK(a) determination by CE of early phase compounds can easily be performed with a very small quantity of material and in addition with insoluble compounds. pK(a) values, similar to those earlier observed by potentiometric titration or computational calculations, were obtained. The reported technique using CE can easily be automated and is able to cope with the high throughput needed at the screening stage of lead optimisation.