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.
Keywords: cyclodextrins; macromolecular pharmacokinetics; pharmaceutical adjuvants.
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