Solvent effect on the photolysis of 5‐fluorouracil: A kinetic study

Abstract

A photodegradation study of 5-fluorouracil (5-FU) has been carried out in the water (pH 7.0) and organic solvents (chloroform, ethyl acetate, acetone, 1butanol, 1-propanol, ethanol, methanol, and acetonitrile) using developed and validated high-performance liquid chromatography (HPLC) method. The test method was found to be simple, accurate (% recovery, 100.25%-101.08%), precise (%RSD < 2.00), and sensitive. The apparent first-order rate constants are in the range of 0.85 (chloroform) to 4.25 × 10 −4 min −1 (water). The values obtained for k obs were found to be linear as a function of the dielectric constant indicating the involvement of the dipolar intermediate in the reaction. The increase in the rate of degradation of this intermediate is enhanced by the polarity of the medium. Rates of photolysis for 5-FU show a linear relationship with the solvent acceptor number (AN) which indicates the degree of solute-solvent interaction. The values of k obs were found to be linear to the inverse of the viscosity of the medium due to the diffusion-controlled process.

Photolysis of tolfenamic acid in aqueous and organic solvents: a kinetic study

“…A correlation between the effect of solvent viscosity on the rates and mechanism of chemical reactions with certain drugs has been reported. 35,58,61,78,81,[86][87][88] A similar viscosity effect was observed when the photodegradation of fenamates was found to lower with an increase in medium viscosity. 89,90 The temperature of the medium plays a vital role in the viscosity effect on the reaction rate.…”

“…This property of solvents may affect the reaction or photolysis rate. 58,78,81 In the present study, a correlation has been made between the apparent first-order rate constants ( k obs ) of TA (Table 2) and the AN of highly structured protic solvents, i.e. , above 25 (Table 2).…”

“…Depending upon the solute-solvent interaction, various solvent characteristics may directly or indirectly affect drug stabilization or degradation. 58,[66][67][68][78][79][80][81] In the present study, four commonly used protic (alcohols) and a polar aprotic organic solvent (acetonitrile) have been employed to study their impact on the photodegradation of TA. The solvents have been selected based on their common lab usage, easy availability, and physicochemical characteristics like dielectric constant, viscosity, acceptor number, ionization potential, and density.…”

“…45,47,58,78 Any change in the dielectric constant value of a solvent may alter the activation energy, thus affecting the degradation rates. 46,58,78,81 A correlation has been made between the apparent rst-order rate constants of TA (Table 2) and the solvent dielectric constants (Table 2), and the plot is shown in Fig. 4.…”

“…75 A similar effect has also been observed previously in drugs like riboavin, 58 uoroquinolones, [66][67][68] and 5-uorouracil. 81 Based on these ndings, it is suggested that using a combination of appropriate solvents for TA may result in comparatively better stability.…”