Dermatopharmacokinetics of different formulation and preparation of dexamethasone acetate creams in nude mouse / 中国药学杂志

ABSTRACT

OBJECTIVE: To study the dermatopharmacokinetics of dexamethasone acetate by administering three different formulation and preparationcreams on skin of nude mouse and discuss the application prospect of the method. METHODS: At 0, 0.25, 0.75, 1.75, 3, 5, 8, 12, 24 h after administered dexamethasone acetate cream about 0.025 g on the back of the nude mice, the excess formulation was gently removed. Then mice were sacrificed at the chosen contact time points. Skin samples were immediately excised from the fixed area of skin and weighed. Both compounds were precipitated from skin homogenate with methanol. The concentrations of dexamethasone acetate in skin were analyzed by using LC-ESI-MS method. The pharmacokinetics parameters were calculated and the percutaneous absorption process in skin of nude mouse was evaluated. RESULTS: This determination method does not interfere with endogenous substances. Calibration curves were linear over the range of 0.052 4-5.24 μg · mL-1. The mean recovery was in the ranges of 89.95%-95.97%. The intra-run relative standard deviations were less than 15%. All the results showed there were no stability related problems during the samples' routine analysis. DMSO can increase the AUC value of dexamethasone acetate, coarse granularity and crystal of cream may decrease the AUC value of dexamethasone acetate. CONCLUSION: This method is fast, sensitive, accurate with good recovery, reproducibility and low detection limited, which can be successfully applied to determine the concentration of dexamethasone acetate in skin and study the dermatopharmacokinetics of nude mouse. This in vivo time-share sampling method can be used in preclinical evaluation and screening the dermatopharmacokinetics of topical drugs.