Validated stability‐indicating derivative and derivative ratio methods for the determination of some drugs used to alleviate respiratory tract disorders and their degradation products

Abstract

Derivative and derivative ratio methods are presented for the determination of butamirate citrate, formoterol fumarate, montelukast sodium, and sodium cromoglycate. Using the second derivative ultraviolet (UV) spectrophotometry, butamirate citrate and formoterol fumarate were determined by measuring the peak amplitude at 260.4 and 261.8 nm, respectively, without any interference of their degradation products. Butamirate citrate degradation product, 2-phenyl butyric acid, was determined by the measurement of its second derivative amplitude at 246.7 nm where butamirate citrate displays zero crossing. Formoterol fumarate degradation product, desformyl derivative, could be evaluated through the use of the first derivative at peak amplitude of 264.8 nm where interference of formoterol fumarate is negligible. In the first mode, the zero-crossing technique was applied at 305 nm for the determination of montelukast sodium in the presence of its photodegradation product, cis-isomer. The derivative of ratio spectra of montelukast sodium and its cis- isomer were used to determine both isomers using the first derivative of the ratio spectra by measuring the amplitudes of the trough at 305 nm and the peak at 308 nm, respectively. The later technique was also used for the determination of a ternary mixture of sodium cromoglycate and its two degradation products using zero-crossing method. In the derivative ratio spectra of the ternary mixture, trough depths were measured at 271.6, 302.8 and 302.2 nm, using the second, the first, and the second mode to evaluate sodium cromoglycate, degradation product (1) and degradation product (2), respectively. All the methods were applied successfully to the pharmaceutical preparation and were validated according to ICH guidelines.