Wang Shixiao, Wang Yang, Gao Shuang, Zhang Yuanyuan, Wang Hanpei, Zhao Longshan, Bi Kaishun, Wang Shaojie, Chen Xiaohui
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang 110016, China.
Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, Shenyang Pharmaceutical University, Shenyang 110016, China.
J Pharm Anal. 2017 Dec;7(6):406-410. doi: 10.1016/j.jpha.2017.07.004. Epub 2017 Jul 8.
A simple, rapid and sensitive method based on an ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed and validated for the determination of pimavanserin in rat plasma. The analyte was extracted by protein precipitation with methanol and separated on an ACQUITY BEH C column (100 × 2.1 mm, 1.7 µm; Waters, USA), with an isocratic elution of acetonitrile-water containing 10 mM ammonium acetate (70:30, v/v), at a flow rate of 0.2 mL/min for 2.5 min. The analyte and clarithromycin (the internal standard) were detected and quantified in positive ion mode using multiple reaction monitoring transitions at / 428.2 → 223.0 for pimavanserin and / 748.5 → 589.5 for clarithromycin. Relative coefficient () for the calibration curve was more than 0.9980. The intra-day and inter-day precisions (relative standard deviation, RSD%) were less than 13.3% and 10.5%, respectively, and the accuracy (relative error, RE%) was within ± 11.5%. The analytical method was successfully applied to a routine pharmacokinetic study of pimavanserin in rats after oral administration at the dose of 10 mg/kg.
已开发并验证了一种基于超高效液相色谱 - 串联质谱法（UPLC - MS/MS）的简单、快速且灵敏的方法，用于测定大鼠血浆中的匹莫范色林。通过用甲醇进行蛋白沉淀来提取分析物，并在ACQUITY BEH C柱（100×2.1 mm，1.7 µm；美国沃特世公司）上进行分离，采用含10 mM醋酸铵的乙腈 - 水等度洗脱（70:30，v/v），流速为0.2 mL/min，洗脱时间为2.5分钟。在正离子模式下，使用多反应监测转换对分析物和克拉霉素（内标）进行检测和定量，匹莫范色林的转换为 / 428.2 → 223.0，克拉霉素的转换为 / 748.5 → 589.5。校准曲线的相关系数（）大于0.9980。日内和日间精密度（相对标准偏差，RSD%）分别小于13.3%和10.5%，准确度（相对误差，RE%）在±11.5%以内。该分析方法成功应用于大鼠口服10 mg/kg剂量匹莫范色林后的常规药代动力学研究。
