School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, P. R. China.
School of Medical Devices, Shenyang Pharmaceutical University, Shenyang, P. R. China.
J Sep Sci. 2021 Jul;44(14):2680-2692. doi: 10.1002/jssc.202100141. Epub 2021 Jun 24.
Hydroxypropyl-β-cyclodextrin, which possesses a high water solubility and low hemolycity, is widely used as a solubilizer and an excipient. It had also been reported that hydroxypropyl-β-cyclodextrin has the activity of regulating lipid homeostasis. In order to further understand the metabolism, the primary focus was to establish a quantitative method for hydroxypropyl-β-cyclodextrin. The analytes were extracted from plasma by protein precipitation with methanol and then carried out on a Waters CORTECS T3 column in the gradient elution of pure water and methanol. Finally, liquid chromatography-tandem mass spectrometry was applied in multiple reaction monitoring mode to complete the quantitative analysis of hydroxypropyl-β-cyclodextrin. This validated method had been successfully applied to investigate the interaction between hydroxypropyl-β-cyclodextrin and butylphthalide in vivo by optimizing the extraction reagent, simplifying the experimental procedure, and improving the sensitivity while considering the difference of drug chemical properties. Results showed that the inclusion of hydroxypropyl-β-cyclodextrin with butylphthalide significantly improved the pharmacokinetic behavior of free body hydroxypropyl-β-cyclodextrin and 3-n-butylphthalide in vivo. It had been implied that the metabolism of hydroxypropyl-β-cyclodextrin and the drug active ingredients could impact each other. It will help better application of hydroxypropyl-β-cyclodextrin and the developed method might lay the foundation for development of hydroxypropyl-β-cyclodextrin as a treatment drug for brain diseases.
羟丙基-β-环糊精具有高水溶性和低溶血活性，广泛用作增溶剂和赋形剂。据报道，羟丙基-β-环糊精具有调节脂质动态平衡的活性。为了进一步了解其代谢情况，研究的重点是建立一种定量测定羟丙基-β-环糊精的方法。采用甲醇沉淀蛋白法从血浆中提取分析物，然后在 Waters CORTECS T3 柱上进行梯度洗脱，以纯水和甲醇为洗脱液。最后，采用液相色谱-串联质谱法（MRM）进行定量分析。该方法经过验证，成功应用于优化提取试剂、简化实验步骤、提高灵敏度，同时考虑药物化学性质差异，考察羟丙基-β-环糊精与丁基苯酞在体内的相互作用。结果表明，羟丙基-β-环糊精与丁基苯酞包合后，可显著改善游离体羟丙基-β-环糊精和 3-正丁基苯酞在体内的药代动力学行为。这表明羟丙基-β-环糊精的代谢和药物活性成分可能相互影响。这将有助于更好地应用羟丙基-β-环糊精，所建立的方法可能为将羟丙基-β-环糊精开发为治疗脑部疾病的药物奠定基础。
