Successive ratio subtraction as a novel manipulation of ratio spectra for quantitative determination of a mixture of furosemide, spironolactone and canrenone

Abstract

Furosemide and spironolactone are commonly prescribed antihypertensive drugs. Canrenone is the main degradation product and main metabolite of spironolactone. Ratio subtraction and extended ratio subtraction spectrophotometric methods were previously applied for quantitation of only binary mixtures. An extension of the above mentioned methods; successive ratio subtraction, is introduced in the presented work for quantitative determination of ternary mixtures exemplified by furosemide, spironolactone and canrenone. Manipulating the ratio spectra of the ternary mixture allowed their determination at 273.6nm, 285nm and 240nm and in the concentration ranges of (2-16μgmL^-1), (4-32μgmL^-1) and (1-18μgmL^-1) for furosemide, spironolactone and canrenone, respectively. Method specificity was ensured by the application to laboratory prepared mixtures. The introduced method was ensured to be accurate and precise. Validation of the developed method was done with respect to ICH guidelines and its validity was further ensured by the application to the pharmaceutical formulation. Statistical comparison between the obtained results and those obtained from the reported HPLC method was achieved concerning student's t-test and F ratio test where no significant difference was observed.

Keywords: Canrenone; Furosemide; Spironolactone; Successive ratio subtraction.