Development a LC-MS/MS method to simultaneous quantitative analysis macromolecular pharmaceutical adjuvant 2-hydroxypropyl-β-cyclodextrin and active pharmaceutical ingredients butylphthalide in rat plasma.

Hydroxypropyl-β-cyclodextrin, possessing higher water solubility and lower hemolytic, was widely used as solubilizer and excipient. It had also been reported that hydroxypropyl-β-cyclodextrin has the activity of regulating lipid homeostatic. 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 Waters CORTECS T3 column in gradient elution of pure water and methanol. Finally, LC MS/MS was applied in MRM 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 HP-β-CD and NBP in vivo. It had been implied that the metabolism of hydroxypropyl-β-cyclodextrin and the drug active ingredients could impact on 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. This article is protected by copyright. All rights reserved.