Development of a MECK system applied to the quality control of ursodeoxycholic acid in pharmaceutical formulations and raw material

BOSCOLO, O; FLOR. S.; MARTINEFSKI M; TRIPODI V.; LUCANGIOLI S.

Congreso; 19th Latin American Symposium on Biotechnology, Biomedical, Biopharmaceutical and Industrial Applications of Capillary Electrophoresis and Microchip Technology (LACE); 2013

Ursodeoxycholic acid (UDCA), also known as ursodiol, its a secondary bile acid which is synthesized in the liver. UDCA lowers the cholesterol content of bile by Reducing hepatic synthesis and reabsorption by the gut. Bile acids are derivatives acid hydroxylated 5β-cholan-24-oic acid, which are characterized by the absence of chromophore groups in its structure, which results in a low absorption in the UV-visible region. In UDCA raw material may be present as impurities other bile acids, some of them toxic, like lithocholic acid (LCA), and others associated with numerous side effects such as chenodeoxicholic acid (CDCA). UDCA official monograph in USP Pharmacopeia describe the determination of related compounds such as CDCA and LCA by thin layer chromatography (TLC), where each impurity limit should be not more than 1.5% and 0.05% respectively. Therefore the aim of this study was to optimize an analytical methodby electrokinetic chromatography using cyclodextrins andmicellar agents for determination of ursodeoxycholic acid and its impurities in pharmaceutical formulations and raw material. The electrophoretic system consisted of 50 mM SDS, 5 mM β-cyclodextrin, 5 mM hydroxypropyl-β-cyclodextrin, 0.5 mM borate/ 0.5 mM phosphate buffer, pH: 7.0 with 10% acetonitrile. A capillary of 60 cm length (50 cm to detector) and 75 µm i.d. was used  and, the applied voltage was 28 kV, the working temperature of 40˚C and 195 nm wavelength were applied. The sample wasdissolved in 0.1 Mpotassium hydroxide and 3% sulfated β-cyclodextrin in 0.5 mM borate/ 0.5 mM phosphate buffer. The developed method is fast, simple and useful for the determination of ursodeoxycholic acid and its impurities, providing a method suitable to the quality control in raw materials as well as in pharmaceutical formulations.