HPLC – Quality by Design Approach for Simultaneous Detection of Torsemide, Spironolactone and Their Degradant Impurities

Abstract

A simple, highly robust (quality by design (QbD) approach), precise and accurate method using high performance liquid chromatography coupled to mass spectrometry has been established for the simultaneous separation, identification and quantitation of a Torsemide (TOR), spironolactone (SPI) and their degradant impurities. The chromatographic separations of drugs and impurities were achieved on a inertsil ODS-3 µm C18, 150 mm × 4.6 mm, while the isocratic elution using a ternary mobile phase mixture of methanol, acetonitrile and water (5:3:2 v/v/v) at a flow rate of 0.2 mL/min was adopted for achieving optimum separations. The quantitation of torsemide and spironolactone was accomplished by UV detection at 254 nm and identification of the degradants were done by comparing identical mass in mass spectrometer. The recoveries of the torsemide and spironolactone were obtained higher than 98 % with good validation parameters; linearity (r2>0.994), LOD and LOQ was 10 and 33 ng for TOR and 75 and 248 ng for SPI respectively. The quality by design (QbD) approach has been successfully utilized to prove the method is robust even deliberate changes in critical parameters.

Keywords

• quality by design
• hplc
• torsemide
• spironolactone
• degradant impurity