Multivariate optimisation of a cyclodextrin-assisted-capillary zone electrophoretic method for the separation of torasemide and its metabolites

In this work, a rapid cyclodextrin-assisted capillary electrophoretic method is developed for the separation of the diuretic torasemide and three of its metabolites. Both fractional factorial and central composite designs were employed to optimise the separation method. The factors studied were pH, concentration of methyl-β-cyclodextrin, concentration of the background electrolyte and percentage of acetonitrile as organic modifier. Monitored response was a composite quality response (Q*) which balanced conflicting normalized responses, such as resolution and migration time. Optimal separation of the four studied compounds was achieved in less than 6.5 min, using an electrolyte of 60 mM borate buffer with no organic modifier and 25 mM methyl-β-cyclodextrin concentration adjusted to pH 8.0 at a potential of 30 kV. Detection wavelength and temperature were 197 nm and 20 °C respectively. This work means a significant improvement with regard to a previous separation method for these compounds developed in our laboratory.