Serge Rudaz

The proportion of counterfeit medicines has increased dramatically. Combatting this issue is complex, and various levels of action are necessary. The quality control (QC) of imported batches using simple, reliable, and cost-efficient analytical approaches is vital. Capillary electrophoresis (CE) is becoming important because the analysis is achieved in a capillary with small dimensions, and is usually filled with an aqueous buffer. No organic solvent is required and injection volumes are in the nanolitre range, which is convenient because of the low availability of reference substances and reduces the environmental impact. CE is now recognized by numerous Pharmacopeia and can be used for counterfeit and substandard characterization as a validated analytical procedure that adheres to international guidelines.

A new method to optimize liquid chromatography (LC) methods using a Quality by Design (QbD) approach is presented. This method is based on the use of design of experiments (DOE) and independent component analysis (ICA) to accurately estimate the modeled responses (that is, the retention times at the beginning, the apex, and the end) of each peak, even for coeluted peaks. This method was applied to the optimization of the separation of nine compounds in a mixture, yielding the design space and the demonstration of robustness of the method.

Very short columns filled with 1.9 µm particles were evaluated for the ultra-fast analysis of pharmaceutical formulations. Local anæsthetic, mydriatic and anti-hypertensive agents were chosen as analytes and a method was developed and validated for each of these substances, according to ICH guidelines. Excellent quantitative performance was obtained using an optimized chromatographic system that reduces the importance of extra-column effects and cuts the analysis time to less than 15 s.