Abstract:
The amounts of methicillin remaining in the buffered solution over the pH range 1.5—9.1 after the period of storage have been determined by visible spectrophotometry in the form of ferric-hydroxymate complex from standpoint of chemical kinetics. The linear relation of logarithm of concentration of methicillin against time might be considered as that the degradative reaction of methicillin is a first-order reaction at a fixed pH value. In aqueous solution the methicillin can occur in two different forms, i.e., as the ionized form and the unionized acid form. The ratio of the concentration of the ionized methicillin to that of its unionized form changes with variation of the pH value and the hydrolysis of them are catalyzed by H+, H
2O and OH
- respectively. The decomposition of methicillin may be accounted for by the six rate constants of bimolecular reaction and the dissociation constant of methicillin. Judging from the rate-pH profile and its theoretical analysis the rate (hr
-1) of reaction over the whole pH range at 35℃ can be practically represented by the following equation:
k=3.39×10
2H
+ /1+1.59×10
-3/H
++2.02×10
3H
++2.24×10
-4+3.02×10
3OH
-/1+H
+/1.59×10
-3 A good agreement was obtained between the calculated curve and the experimental curve in pH value less than 5.6 and more than 8.5. The difference between calculated and experimental values may be considered to be due to the effect of the buffer components. In the rate-pH curve of methicillin it will be noted that at the lower pH region (pH 3.53) and at the higher pH regions (pH 9.1) the logarithm of the apparent rate constant is a linear function of pH value with a slop of near -1 or +1.It may be considered that these correspond to the reactions between ionized form and H
+ with a bimolecular velocity constant (
k4) of 2.02×10
3 (1.mol
-.hr.
-1) and between the ionized form and OH
- with bimolecular velocity constant (
k6) of 3.02×10
3. The values of
k4 and
k6 obtained at 35℃, 45℃, 55℃, are given.From the linear relation between log
k4 and the reciprocal of absolute temperature and between log
k6 and the reciprocal of absolute temperature the Arrhenius equations for the reactions were obtained as follows: log
k4=- 4.41×10
3/
T+17.6 log
k6=- (4.66×10
3/
T+18.6 The half-life of methicillin at pH 1.50 and 35℃ experimently was found to be four minutes while at pH 6.40 and 35℃, 224 hours. The pH of the minimum rate of degradation of methicillin is 6.75 at 35℃, 6.95 at 25℃ and 7.04 at 20℃.