Anaerobic stability of aqueous physostigmine solution.
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.
School of Pharmacy, National Defense Medical Center, Taipei, Taiwan.
J L
JL
Chen
M K
MK
Yeh
C H
CH
Chiang
D000693:Anaerobiosis; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007211:Indoles / Q000138:chemical synthesis / Q000737:chemistry; D007700:Kinetics; D010100:Oxygen / Q000737:chemistry*; D010830:Physostigmine / Q000737:chemistry*; D012996:Solutions; D013056:Spectrophotometry, Ultraviolet; D013696:Temperature; D013816:Thermodynamics; D014867:Water / Q000737:chemistry
D002800:Cholinesterase Inhibitors; D007211:Indoles; D012996:Solutions; D014867:Water; D010830:Physostigmine; C022594:eseroline; D010100:Oxygen