ACCELERATED STABILITY STUDIES ON ROCEPHIN BY HIGH-EFFICIENCY LIQUID-CHROMATOGRAPHY

The stability of Rocephin in aqueous solutions was studied for different pH values in research into accelerated instability. The pH range studied was 2.5, 4.5, 5.5, 6.5, 7.4 and 8.0 adjusted to an ionic strength of .mu. = 0.5; each of these values was subjected to temperatures of 50, 60, 70 and 80.degree. C. From the experimental values found for the concentrations of undegraded Rocephin as a function of time, the degradation process of this cephalosporin evidently follows 1st-order kinetics. The technique used for the determination of Rocephalin was high-efficiency liquid chromatography, using a reverse phase (RP-18) as the stationary phase. Linear relationships were established for each pH studied, between the logarithms of the experimental degradation constants and the reciprocals of the absolute temperatures, obtaining correlation coefficients greater than 0.91. These values were used to calculate the values of the degradation constants, half-lives and expiry date for each pH at temperatures of 37, 20 and -4.degree. C. Simultaneously, the activation energy and the logarithm of the frequency factor were determined, giving average values of 13.11 kcal/mol and 5.62, respectively. The values obtained for the expiry date at 20.degree. C, greater than 7 h for all the pH values, mean that in terms of pH-regulated degradation this antibiotic may be used in the normal perfusion liquids.