KINETIC-STUDY ON THE DEGRADATION OF INDOMETHACIN IN ALKALINE AQUEOUS-SOLUTIONS BY DERIVATIVE ULTRAVIOLET SPECTROPHOTOMETRY

A fourth-order derivative method for monitoring a degradation product is proposed for the kinetic investigation of the alkaline hydrolysis o f indomethacin, where indomethacin co-exists with its degradation prod ucts, A second-order derivative approach for monitoring the parent com pound itself was also examined but showed;limitations. Detection limit s for the second-and fourth-order derivative methods, defined as b + 3 s(b), are 4 x 10(-6) and 2 x 10(-6) mol dm(-3), respectively. In this work the kinetic investigation of the alkaline hydrolysis of indometha cin was carried out at pH levels of 8.0, 9.0 and 10.0, Two sets of rec overy studies, in order to calculate one substance in the presence of the other, gave us 104.0 +/- 0.3% and 96.8 +/- 9.7% (for the second-or der derivatization) and 100.9 +/- 0.9% and 101.4 +/- 1.5% (for the fou rth-order derivative approach) showing that only the latter method can be considered free of interference and is analytically useful, Accele rated studies at higher temperatures have been employed that enable ra pid prediction of the long-term stability of this drug at pH 8.0 (90 d egrees C), 9.0 (35, 40 and 45 degrees C) and 10.0 (20, 26 and 30 degre es C), At pH 9.0 and 10.0 enough data were produced to draw Arrhenius plots and calculate the activation energies for drug decomposition: E( a) = 17 +/- 1 kcal mol(-1) (1 cal = 4.184 J) and 14 +/- 1 kcal mol(-1) , respectively, Kinetic results for k(obs) and t(1/2) at room temperat ure (25 degrees C) were estimated from the Arrhenius plots: k(obs) = 7 .7 x 10(-4) min(-1) and t(1/2) = 900 min at pH 9.0 and k(obs) = 7.3 x 10(-3) min(-1) and t(1/2) = 95 min at pH 10.0. Measurements of absorba nce at a wavelength of 360 nm in the zero-order spectrum of indomethac in were included in our study for the purpose of comparison as well as literature results.