南方医科大学学报

南方医科大学学报 ›› 2020, Vol. 40 ›› Issue (07): 995-1000.doi: 10.12122/j.issn.1673-4254.2020.07.12

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LC-MS/MS法研究瓜蒌缓释微丸在大鼠体内的药代动力学特征

卞莹莹，邹纯才，鄢海燕，孙德考，胡 倩   

  • 出版日期:2020-07-20 发布日期:2020-07-20
  • 基金资助:

LC-MS/MS analysis of pharmacokinetics of 3,29-dibenzoyl karounitriol in rats following administration of Trichosanthes sustained-release pellets

  

  • Online:2020-07-20 Published:2020-07-20

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摘要： 目的 建立高效液相色谱串联质谱法（LC-MS/MS）考察瓜蒌缓释微丸与瓜蒌提取物中3,29-二苯甲酰基栝楼仁三醇（3,29-DK）在大鼠体内不同时间点的血药浓度及药代动力学特征。方法 健康雄性SD大鼠分为2组：瓜蒌缓释微丸组与瓜蒌提取物组，单次灌胃给药后，瓜蒌缓释微丸组在第0、1、2、4、6、8、10、12、18、24、36、48小时眼眶取血；瓜蒌提取物组在第0、15、30、45、60、 90、120、180、240、300分眼眶取血。血浆样品预处理，采用LC-MS/MS法测定瓜蒌缓释微丸组与瓜蒌提取物组血浆中的3,29-DK浓度，建立3,29-DK含量测定标准曲线并进行专属性、最低检测限、精密度及准确度、提取回收率、稳定性、基质效应等方法学考察。测定瓜蒌缓释微丸组和瓜蒌提取物组不同时间点的3,29-DK平均血药浓度，运用Das 2.0软件处理数据，求算药代动力学参数，采用SPSS 26.0统计学软件进行统计分析。结果 3,29-DK浓度在0.5 ng/mL~32 ng/mL范围内线性关系良好，方法学验证结果均符合生物样品测定的规定。与瓜蒌提取物组相比较，瓜蒌缓释微丸组3,29-DK的AUC(0-t)、AUC（0-∞）、MRT（0-t）、MRT（0-∞）、t1/2z及Tmax差异具有统计学意义（P<0.05）。结论 瓜蒌缓释微丸提高了药物在大鼠体内的缓释效果，为瓜蒌新剂型的研究提供基础。

关键词: 高效液相色谱串联质谱法, 瓜蒌缓释微丸, 3,29-二苯甲酰基栝楼仁三醇, 药代动力学

Abstract: Objective To study the plasma concentration and pharmacokinetics of 3,29-Dibenzoyl Karounitriol (3,29-DK) from sustained- release pellets and extracts of Trichosanthes at different time points in rats using high-performance liquid chromatography- tandem mass spectrometry (LC-MS/MS). Methods Healthy male SD rats were given a single gavage of Trichosanthes sustained-release pellets or Trichosanthes extract, and orbital blood samples were taken at different time points within 48 h after drug administration in the pellet group and within 5 h in Trichosanthes extract group for determination of the plasma concentrations of 3,29-DK using LC-MS/MS. The standard curve of 3,29-DK content was established, and the specificity, minimum detection limit, precision and accuracy, extraction recovery, stability and matrix effect of LC-MS/MS analysis were assessed. The mean plasms levels of 3,29-DK at different time points after the drug administration were determined and its pharmacokinetic parameters were calculated using Das 2.0 software. Results LC-MS/MS analysis showed a good linearity of 3,29-DK concentration within the range of 0.5-32 ng/mL, and the results of methodological validation confirmed the validity of this method for biological sample determination. Trichosanthes sustained-release pellets and Trichosanthes extract showed significant differences in their AUC(0- t), AUC(0- ∞), MRT(0- t), MRT(0- ∞), t1/2z and Tmax of 3,29-DK after administration in rats (P<0.05). Conclusion Trichosanthes sustained-release pellets are capable of sustained-release of 3,29-DK in rats, and thus provides a basis for the study of new dosage forms of Trichosanthes.

Key words: high-performance liquid chromatography-tandem mass spectrometry, Trichosanthes sustained-release pellets, 3,29- dibenzoyl karounitriol, pharmacokinetics