CB1R部分拮抗剂alisol G的大鼠药动学研究及血脑屏障透过率初评  

Pharmacokinetics and Blood-brain Barrier Permeability of CB1R Partial Antagonist Alisol G in Rats

作　　者：赵静 奚健强[2] 张贝贝 宋定中 程志红 ZHAO Jing;XI Jianqiang;ZHANG Beibei;SONG Dingzhong;CHENG Zhihong(School of Pharmacy,Fudan University,Shanghai 201203;National Pharmaceutical Engineering Research Center,China State Institute of Pharmaceutical Industry,Shanghai 201203)

机构地区：[1]复旦大学药学院,上海201203 [2]中国医药工业研究总院药物制剂国家工程研究中心,上海201203

出　　处：《中国医药工业杂志》2020年第1期95-101,140,共8页Chinese Journal of Pharmaceuticals

摘　　要：建立了UPLC-MS/MS方法测定大鼠血浆及脑脊液中大麻素受体1(CB1R)部分拮抗药泽泻醇G(alisol G)的浓度,评价其血脑屏障透过性。以利莫那班为内标,采用液液萃取前处理方法,色谱柱为ACQUITY BEH C18柱,流动相为甲醇∶0.1%乙酸溶液(90∶10),质谱采用正离子扫描的电喷雾离子源,多反应监测(MRM)模式,对m/z 455.16→m/z383.04(泽泻醇G)、m/z 464.88→m/z364.75(内标)进行定量分析。泽泻醇G血浆样品在10~4000ng/ml、脑脊液样品在4~400 ng/ml范围内线性良好;批内、批间RSD≤10.22%,样品回收率稳定(78.5%~86.5%)、贮存和处理条件下稳定性良好。本方法灵敏、可靠,能准确测定大鼠血浆及脑脊液中的泽泻醇G浓度。大鼠灌胃后血浆中cmax为312.64ng/ml,脑脊液中检测不到原型化合物,表明泽泻醇G不易透过血脑屏障。本研究结果为CB1R部分拮抗药泽泻醇G的后续研究开发提供了重要依据。Alisol G, an ingredient of Chinese medicine Rhizoma Alismatis, is a partial antagonist of cannabinoid receptor 1(CB1 R). Antagonizing CB1 R has significant weight loss and hypolipidemic effects. While CB1 R blockade in central nervous system would arouse some neuropsychiatric side effects, such as anxiety, depression, suicide, etc. The purpose of this study was to establish a UPLC-MS/MS method to determine the concentration of alisol G in rat plasma and cerebrospinal fluid(CSF) after oral administration and then evaluate its blood-brain barrier permeability. With rimonabant as internal standard(IS), the plasma and CSF samples were processed by liquid-liquid extraction and separated on a ACQUITY BEH C18 column with the mobile phase of methanol∶0.1% acetic acid(90∶10). Alisol G and IS were ionized in the positive electrospray ionization(ESI) and monitored via multiple reaction monitoring(MRM) mode at m/z 455.16→m/z 383.04 for alisol G and m/z 464.88→m/z 364.75 for IS, respectively. This method was sensitive and reliable, and could accurately determine the concentration of alisol G in rat plasma and CSF. After intragastric administration, the cmax in rat plasma was 312.64 ng/ml, and no prototype compound was detected in rat CSF. The experimental results showed that alisol G could not pass through the blood-brain barrier, which provided a basis for subsequent research.

关 键 词：泽泻醇G 大麻素受体1 UPLC-MS/MS 药物动力学 血脑屏障透过率 

分 类 号：O657.63[理学—分析化学]