论文部分内容阅读
目的利用裸鼠在体皮肤给药,比较3种不同处方工艺的醋酸地塞米松乳膏皮肤药动学行为,同时探讨裸鼠在体皮肤药动学方法的应用前景。方法选择裸鼠背部皮肤在体涂复方醋酸地塞米松乳膏约0.025 g后,于0、0.25、0.75、1.75、3、5、8、12、24 h后去除残余药物,取皮,称重,甲醇匀浆沉淀蛋白,采用高效液相色谱-电喷雾离子质谱联用法(LC-ESI-MS)测定裸鼠皮肤中的醋酸地塞米松浓度,计算药动学参数,同时对三种乳膏裸鼠经皮吸收的行为进行评价。结果该测定方法没有内源性物质干扰,醋酸地塞米松皮肤匀浆液浓度在0.052 4~5.24μg·m L-1内,线性关系良好。3种浓度的回收率分别是95.97%、89.95%、91.72%,精密度的RSD均<15%,样品的稳定性良好。经测定,处方中含二甲基亚砜(DMSO)能增加醋酸地塞米松的皮肤药动学参数AUC值,而乳膏粒度大、有结晶则减少醋酸地塞米松的皮肤药动学参数AUC值。结论 LC-ESIMS分析方法快速、灵敏、准确,回收率高,重现性好,检测限低,可成功的用于测定醋酸地塞米松在裸鼠皮肤中的浓度,较好地反映醋酸地塞米松在裸鼠皮肤中的经皮吸收行为,裸鼠在体给药分时取样法可用于临床前外用药物的皮肤药动学筛选与评价。
OBJECTIVE: To study the pharmacokinetics of dexamethasone acetate cream in nude mice on skin and to compare the pharmacokinetics of dexamethasone acetate cream on three different prescriptions. Methods The nude mice back skin was coated with 0.025 g dexamethasone acetate cream and the residual drug was removed after 0, 0.25, 0.75, 1.75, 3, 5, 8, , The protein was precipitated with methanol and the concentration of dexamethasone acetate in the skin of nude mice was determined by high performance liquid chromatography-electrospray ionization mass spectrometry (LC-ESI-MS). The pharmacokinetic parameters were calculated. The percutaneous absorption of nude mice was evaluated. Results The determination method did not interfere with endogenous substances. The concentration of dexamethasone acetate in the skin homogenate ranged from 0.052 4 to 5.24 μg · m L-1, and the linearity was good. The recoveries of three concentrations were 95.97%, 89.95% and 91.72%, respectively. The RSDs of precision were all less than 15%. The stability of the samples was good. It was determined that the prescription contains dimethyl sulfoxide (DMSO) can increase dexamethasone acetate skin pharmacokinetic parameters AUC value, while the cream particle size, crystallization is reduced dexamethasone acetate skin pharmacokinetic parameters AUC value. Conclusion The LC-ESIMS method is rapid, sensitive, accurate, high recovery, good reproducibility and low detection limit. It can be successfully used to determine the concentration of dexamethasone acetate in the skin of nude mice, The transdermal absorption of mesomatsu in the skin of nude mice, and the time-sampling method of in vivo administration of nude mice can be used to screen and evaluate the skin pharmacokinetics of preclinical topical drugs.