Abstract
Abstract: :
Purpose:To determine the stability of bimatoprost, latanoprost, and travoprost under thermal stress. Methods:Reference samples of known purity and concentration of bimatoprost, latanoprost, and travoprost were used to prepare standard curves. Commercially available bimatoprost, latanoprost, and travoprost were used and kept in their original bottles as distributed by the manufacturers. All external packaging was removed. The bottles were kept in calibrated, non–humidified, light–free incubators maintained at 27º C, 37º C, or 50º C for periods of 3 days, 9 days, 15 days, or 30 days. Three bottles of each drug were analyzed for each combination of temperature and duration of stress. To simulate patient use, the capped bottles were inverted, and then left uncapped for one minute daily. No drops were expelled. At the end of the stressing period the drugs were frozen at –80º C, in their original bottles. Bimatoprost was analyzed using high–pressure liquid chromatography with an ultraviolet detector at 210nm. Latanoprost was analyzed with LC/MS using selected reaction monitoring. Results:For bimatoprost, in all stress combinations of temperature and duration, native drug concentration ranged from 101 to 115% of the labeled concentration. Off–the–shelf control bottles had a concentration of 99.2% of the labeled concentration. For latanoprost, in all stress combinations of temperature and duration, the concentration of native drug ranged from 96.6 to 120% of the labeled concentration. Off–the–shelf control bottles had 115.4% of the labeled concentration. For latanoprost stressed at 50º C, degradation occurred at the rate of –0.26 µg/mL/day. No significant degradation occurred at other temperatures. Results for travoprost are pending. Conclusions:Under the conditions of stress tested in this study, bimatoprost remained stable for all conditions tested. The higher than expected concentrations for the stressed samples are likely a result of evaporation. For latanoprost, significant degradation only occurred in samples stressed at 50º C.
Keywords: pharmacology • drug toxicity/drug effects