【摘要】 目的采用微透析技术,考察盐酸去甲异波尔定（norisoboldine hydrochloride,NOR·HCl）乳膏大鼠经皮给药后的药物浓度变化,评价其透皮释药性能。方法建立NOR·HCl的UPLC-MS/MS含量测定方法,并进行专属性、稳定性、精密度及基质效应等方法学考察。大鼠腹部脱毛处理,局部给药,应用微透析技术,结合UPLC-MS/MS测定皮肤透析液中药物质量浓度,以NOR·HCl生理盐水溶液作为对照,比较其与NOR·HCl乳膏的药物浓度-时间曲线差异。结果以青藤碱（m/z 330→239）为内标,流速0.4 mL·min^-1,柱温45℃,乙腈-0.1%甲酸为流动相梯度洗脱,多反应监测（MRM）模式检测,NOR·HCl（m/z 314→265）在1～520 ng·mL^-1范围内线性关系良好,R²=0.997,方法学RSD均<10%,基质效应在86.89%～100.80%,符合标准。NOR·HCl乳膏和生理盐水溶液给药后,微透析接受液中的药物达峰浓度(C_max)分别为（110.60±22.28）和（37.63±1.01）ng·mL^-1,药时曲线下面积(AUC_0-10)分别为（511.17±4.78）和（88.20±1.45）ng·h·mL^-1。与生理盐水溶液相比,NOR·HCl乳膏可将药物透过皮肤的C_max提高2.94倍,AUC_0-10提高5.80倍。结论在体微透析技术可用于评价NOR·HCl乳膏的透皮释药性能;乳膏可显著提高NOR·HCl的皮肤透过量。更多还原

【Abstract】 Objective To investigate the changes in concentration of norisoboldine hydrochloride（NOR HCl） cream after transdermal administration in rats and evaluate transdermal drug release performance of the cream by microdialysis technique. Methods A UPLC-MS/MS method for the determination of NOR·HCl was established, and its specificity, stability, precision and matrix effect were investigated. The NOR·HCl cream was applied onto the bare abdominal skin of the animals. The microdialysis technique and UPLC-MS/MS were used to determine the concentration of the drug, and the drug concentration-time curve was compared between NOR·HCl cream and NOR·HCl normal saline solution. Results Gradient elution was performed with sinomenine（m/z 330→239） as internal standard and acetonitrile-0.1% formic acid as mobile phase at a flow rate of 0.4 mL·min^-1 and a column temperature of 45 ℃. It was shown in multiple reaction monitoring（MRM） that NOR·HCl（m/z 314→265） had good linearity over a range of 1～520 ng·mL^-1, with R²=0.997, methodological RSD<10% and matrix effect of 86.89%-100.80%, which met the standards. After administration of NOR·HCl cream and normal saline solution, the maximal drug concentration(C_max) in microdialysis solution was（110.60±22.28） and（37.63±1.01） ng·mL^-1 respectively and area under the concentration-time curve(AUC_0-10) was（511.17±4.78） and（88.20±1.45） ng·h·mL^-1 respectively. Compared with normal saline solution, NOR·HCl cream increased C_max by 2.94 times and AUC_0-10 by 5.80 times.Conclusion The in vivo microdialysis technique can be used to evaluate the transdermal drug release performance of NOR·HCl cream and cream can significantly increase transdermal release of NOR·HCl.更多还原