Chen_2000_Drug.Dev.Ind.Pharm_26_1007

The anaerobic stability of physostigmine was studied in this report. Physostigmine and two important degradants, eseroline and rubreserine, were identified by a high-performance liquid chromatography (HPLC) system using a photodiode array detector and a UV detector at the retention times of 12.4, 9.2, and 7.9 min. Under anaerobic treatment, the minimum degradation rate constant was found at pH 3.4, evaluating from pH-rate profiles at 45 degrees C, 55 degrees C, and 70 degrees C with the pH range 2.4-6.8. The degradation of physostigmine was suggested as specific acid-base catalysis. Anaerobic activation energies of KH, K(OH), and Kobs were 9.4, 8.3, and 17.9 kcal/mol, respectively. The ratios of observed aerobic and anaerobic rate constants were 2-33 at 88 degrees C, which had a trend to increase ratios as pH increased in the range 2.4-5.2. The shelf life of physostigmine solution was estimated to be 4 years at room temperature under anaerobic conditions at pH 3.4.