Ha. Archontaki, KINETIC-STUDY ON THE DEGRADATION OF INDOMETHACIN IN ALKALINE AQUEOUS-SOLUTIONS BY DERIVATIVE ULTRAVIOLET SPECTROPHOTOMETRY, Analyst, 120(10), 1995, pp. 2627-2634
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.