LINEAR AND NONLINEAR COMPETITION PLOTS IN THE DEOXYRIBOSE ASSAY FOR DETERMINATION OF RATE CONSTANTS FOR REACTION OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS WITH HYDROXYL RADICALS
N. Parij et al., LINEAR AND NONLINEAR COMPETITION PLOTS IN THE DEOXYRIBOSE ASSAY FOR DETERMINATION OF RATE CONSTANTS FOR REACTION OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS WITH HYDROXYL RADICALS, Free radical research, 23(6), 1995, pp. 571-579
Performing the deoxyribose (DR) assay for determination of the rate co
nstants for reaction of non steroidal antiinflammatory drugs with hydr
oxyl radicals led to some unusual competition plots. The molecules fro
m the arylpropionic family of drugs: ibuprofen, flurbiprofen, ketoprof
en and naproxen produced the linear relationship. However, acemetacin,
diclofenac Na, flufenamic acid, indometacin, niflumic acid, tolmetin
Na and sulindac presented non linear competition plots manifesting at
relatively low drug concentrations. This effect was corrected by incre
asing DR concentrations from 2.8 mM to 15 mM. The modification did not
affect rate constants values for those derivatives which already pres
ented a linear plot at 2.8 mM, but allowed to calculate rate constants
for other compounds. It is suggested that the experimental conditions
have to be adapted particularly for those derivatives with a relative
ly high rate constant for reaction with the radical species. The oxica
m derivatives (tenoxicam and piroxicam) presented another kind of devi
ation that revealed a prooxidant effect in this system: non linear plo
ts were also observed at relatively low drug concentrations, but in th
e opposite direction than for the other molecules. This last effect wa
s independent of DR concentration but could be corrected by increasing
ascorbate concentration in the system.