FORCED DEGRADATION STUDY OF TORASEMIDE: CHARACTERIZATION OF ITS DEGRADATION PRODUCTS

Abstract

Torasemide was subjected to forced degradation studies. Stress conditions were varied concerning hydrolysis (acid, base, and neutral), oxidation, photolysis, and thermal degradation in order to identify the potential degradation products and consequently establish the possible degradation pathways and intrinsic stability of the drug. The study was performed according to ICH guidelines and drug was found to be relatively stable in the solid form. It showed that torasemide degraded significantly under acidic, neutral and alkaline conditions and resulted in formation of degradation product R2. When temperature was increased the degradation was accelerated. Also, the drug showed slight instability under extreme oxidative stress conditions which resulted in formation of two degradation products in total. The drug and degradation products have been separated employing gradient elution method on Zorbax SB C₁₈ analytical column. To characterize the degradation products LC–MSⁿ was applied. The mass fragmentation pattern was established using single quadrupole and ion trap mass analyzers. Finally, the most possible degradation mechanism of torasemide in different experimental conditions was proposed.

Keywords:

• degradation pathway
• forced degradation study
• HPLC-DAD
• HPLC-MS/MS
• possible degradation products
• torasemide

ACKNOWLEDGMENT

These results are part of the project No. 172033, financed by the Ministry of Education and Science of the Republic of Serbia.