Triptolide, a major active ingredient of Tripterygium wilfordii Hook F, provides anti-inflammatory and neuroprotective activities. In this study, a microwave-assisted stable isotope labeling derivatization-magnetic dispersive solid phase extraction (MA-SILD-MDSPE) combined with ultra-high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) method has been developed for the determination of the triptolide in rat microdialysates. A pair of SILD reagents (d0-/d3-3-N-methyl-2'-carboxyl Rhodamine 6G, d0-/d3-MCR6G) were used to label triptolide in real samples and standards under mild conditions. The introduction of SILD reagents enhanced the sensitivity of MS/MS detection and ensured accurate quantification. A novel molecularly imprinted polymer coating with d0-MCR6G labeled triptolide as template was firstly synthesized by precipitation polymerization method, and used to selectively extract the labeled triptolides from complex matrices. The purified d0-/d3-MCR6G-triptolides were determined by UHPLC-MS/MS analysis. Using the proposed method, a good linearity (R2>0.995), low limits of detection (LOD, 0.45-0.50 pg/mL) and quantification (LOQ, 3.0 pg/mL) were achieved. The intra- and inter-day precision and accuracy were within the acceptable ranges. No significant matrix effect was observed. The derivatization efficiency was more than 96 %. The validated method was successfully applied to a comparative pharmacokinetic study of triptolide synchronously in brain and blood of normal and Alzheimer's disease rats by in vivo microdialysis sampling technique.

中文翻译：

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鼠脑和血液中雷公藤甲素变化的同步测量及其在正常和阿尔茨海默病大鼠的比较药代动力学研究中的应用。

雷公藤甲素是雷公藤雷公藤钩F的主要活性成分，具有抗炎和神经保护作用。本研究开发了一种微波辅助稳定同位素标记衍生化-磁分散固相萃取（MA-SILD-MDSPE）结合超高效液相色谱串联质谱法（UHPLC-MS / MS）的方法大鼠微量透析液中雷公藤甲素的含量测定。在温和条件下，使用一对SILD试剂（d0- / d3-3-N-甲基-2'-羧基若丹明6G，d0- / d3-MCR6G）标记雷公藤内酯。SILD试剂的引入提高了MS / MS检测的灵敏度，并确保了准确的定量。以沉淀聚合法合成了以d0-MCR6G标记的雷公藤甲素为模板的新型分子印迹聚合物涂层，并用于从复杂基质中选择性提取标记的雷公藤甲素。通过UHPLC-MS / MS分析确定纯化的d0- / d3-MCR6G-雷公藤内酯。使用所提出的方法，可以实现良好的线性（R2> 0.995），低检测限（LOD，0.45-0.50 pg / mL）和定量（LOQ，3.0 pg / mL）。日内和日间精度和准确度均在可接受的范围内。没有观察到明显的基质效应。衍生化效率超过96％。验证的方法已成功应用于雷公藤内酯醇在正常人和阿尔茨海默氏病患者的脑和血液中同步进行的比较药代动力学研究