Chiral separation of indapamide enantiomers by capillary electrophoresis

Indapamide is probably the most frequently prescribed diuretic drug, generally being used for the treatment of hypertension. It contains a chiral center in its molecule; is marketed as a racemic mixture; but there are rather few studies regarding the pharmacokinetic and the pharmacological effect differences of the two enantiomers. Our aim was the development of a simple, rapid and precise analytical procedure for the chiral separation of indapamide enantiomers.

In this study capillary zone electrophoresis was used for the enantiomeric separation of indapamide using a systematic screening approach involving different native and derivatized; neutral and charged cyclodextrines as chiral selectors. The effects of pH value and composition of the background electrolyte, capillary temperature, running voltage and injection parameters have been investigated.

After preliminary analysis a charged derivatized CD, sulfobuthyl ether- β-CD, proved to be the optimum chiral selector for the enantioseparation. Using a buffer solution containing 25 mM disodium hydrogenophosphate - 25 mM sodium didydrogenophosphate and 5 mM sulfobuthyl ether- β-CD as chiral selector at a pH - 7, a voltage of + 25 kV, temperature 15°C and UV detection at 242 nm, we succeeded in the separation of the two enantiomers in approximately 6 minutes, with a resolution of 4.30 and a separation factor of 1.08.

Capillary zone electrophoresis using cyclodextrines as chiral selectors proved to be a suitable method for the enantioseparation of indapamide. Our method is rapid, specific, reliable, and cost-effective and can be proposed for laboratories performing indapamide routine analysis.