基于微透析结合UPLC的弩药微乳经皮给药后多成分皮肤药动学研究

Study on the Multi-Component Skin Pharmacokinetics of Crossbow Microemulsion after Transdermal Administration Based on Microdialysis Combined with UPLC

    摘要
  • 摘要:
      目的  考察弩药微乳多成分在家兔皮肤组织中的药动学特征。
      方法  采用UPLC测定绿原酸、苯甲酰新乌头原碱、杠柳毒苷、新乌头碱质量浓度; 采用增量法与减量法探究温度、灌流速度、质量浓度对探针回收率的影响, UPLC测定弩药微乳经皮给药后不同时间点透析液中多成分含量变化, 并用DAS2.0软件处理数据。
      结果  升高温度, 各成分探针回收率逐渐提高; 流速越大, 药物回收率越低, 且回收率与探针周围药物质量浓度关系不大。弩药微乳中绿原酸、苯甲酰新乌头原碱、杠柳毒苷、新乌头碱在皮下组织中的药动学参数Cmax分别为(3.24±0.36)(1.04±0.29)(4.78±2.15)(2.86±0.55)μg·mL-1; AUC0-∞分别为(52.42±30.84)(7.70±3.73)(42.23±13.93)(22.68±12.51)h·μg·mL-1。
      结论  首次采用微透析在体实时取样技术, 建立UPLC检测方法, 对弩药微乳经皮给药后多成分皮肤药动学进行研究, 为弩药微乳后续的考察及应用提供参考。

     

    Abstract:
      OBJECTIVE  To investigate the pharmacokinetic characteristics of crossbow microemulsion in rabbit skin.
      METHODS  The concentrations of chlorogenic acid, benzoyl new aconitine, periplocin and new aconitine were determined by UPLC. The effects of temperature, perfusion speed and mass concentration on the recovery rate of the probe were investigated by incremental and decrement methods, the changes of multi-component content in the dialysate at different time points after transdermal administration of crossbow microemulsion were determined by UPLC, and DAS 2.0 software was used to process the data.
      RESULTS  The recovery rate of the probe increased with increasing temperature, and the higher the flow rate, the lower the recovery rate. The pharmacokinetic parameters of chlorogenic acid, benzoyl new aconitine, periplocin and new aconitine in microemulsion Cmax were (3.24±0.39) (1.04±0.29) (4.78 ± 2.15) (2.86 ± 0.55) μg·mL-1, respectively, and in AUC0-∞ were (52.42 ± 30.84) (7.70 ± 3.73) (42.23 ± 13.93) (22.68 ± 12.51) h·mg·mL-1, respectively.
      CONCLUSION  A real-time in vivo microdialysis sampling technique was first used and a UPLC detection technique was established to study the skin pharmacokinetics of multi-components of crossbow microemulsion after transdermal administration, which provides a reference for the follow-up investigation and application of crossbow microemulsion.

     

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