An LC/MS quantitative and microdialysis method for cyclovirobuxine D pharmacokinetics in rat plasma and brain: The pharmacokinetic comparison of three different drug delivery routes

作者：Wei, Jia bao; Lai, Qiao; Shumyak, Stepan P; Xu, Lan fang; Zhang, Chen xue; Ling, Jia jun; Yu, Yang^*

来源：Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 2015, 1002: 185-193.

DOI：10.1016/j.jchromb.2015.08.022

• Microdialysis
• LC-MS/MS
• Different drug delivery routes
• Rat brain and plasma pharmacokinetic

To explore the brain-targeting of cyclovirobuxine D(CVB-D) after administered intranasally, the pharmacokinetics of CVB-D via three different drug delivery routes: intragastric (i.g.), intranasal (i.n.), and intravenous (i.v.) in rat brain and blood was compared. Firstly, an in vivo microdialysis method for sampling CVB-D in both plasma and brain of the rat was established. Secondly, a liquid chromatography-tandem mass spectrometry method has been developed and validated for determination of CVB-D in microdialysis samples. For plasma and brain microdialysis samples, liquid-liquid extraction was used and donepezil was chosen as internal standard. Both were followed by HPLC separation and positive electrospray ionization tandem mass spectrometry detection (ESI-MS/MS). Chromatographic separation was achieved on a agilent C18 column with a mobile phase of methanol-water (50:50, v/v) (pH 3.2) containing 0.1% formic acid and 5 mM ammonium acetate. Mass spectrometric detection in the positive ion mode was carried out by selected reaction monitoring (MRM) of the transitions at m/z 403.4 -> 372.3 for CVB-D and m/z 380.2 -> 243.1 for donepezil (IS). Good linearities were obtained in the range of 10-4000 ng/mL in rat microdialysates for CVB-D. The lowest limit of quantitation was 5 ng/mL, with an extraction recovery >75%, and no significant matrix effects. Intra- and inter-day precisions were all <15% with accuracies of 97.26-116.20%. All of which proved that the established method was successfully applied to the pharmacokinetic study of CVB-D. Simultaneously, brain uptake and pharmacokinetic studies were performed by determination of CVB-D concentration in blood and brain respectively for CVB-D i.g., i.n. and i.v.. Results showed that the intranasal CVB-D could improve brain targeting and had advantages for direct nose to brain transport of CVB-D when compared with injection and oral delivery routes, which indicates that intranasal administration of CVB-D could be a promising approach for the treatment of cerebrovascular disease.

• 出版日期2015-10-1
• 单位广州中医药大学