人血浆中替曲朵辛血药浓度测定方法的初步建立与药动学应用  

Preliminary Establishment of the Method for Determination of Tetrodotoxin in Human Plasma and the Pharmacokinetics Application

作　　者：葛庆华[1] 项苗苗[1] 宣坚钢 李周[1] 康修远 GE Qinghua;XIANG Miaomiao;XUAN Jiangang;LI Zhou;KANG Xiuyuan(National Advanced Medical Engineering Research Center,China State Institution of Pharmaceutical Industry,Shanghai 201203;Jiangsu Hongjintian Pharmaceutical Co.,Ltd.,Taizhou 225316)

机构地区：[1]中国医药工业研究总院医药先进制造国家工程研究中心,上海201203 [2]江苏宏锦天药业有限公司,江苏泰州225316

出　　处：《中国医药工业杂志》2024年第6期844-850,共7页Chinese Journal of Pharmaceuticals

基　　金：上海市科委工程技术研究中心专项(17DZ2252900)。

摘　　要：建立了LC-MS/MS法测定人血浆中的替曲朵辛(1)。采用Waters Atlantis HILIC Silica色谱柱(2.1 mm×100 mm,3μm),流动相由乙腈、水和乙酸组成,流速为0.40 m L/min,柱温为40℃,进样量为10μL。该方法的线性范围为0.02~5ng/m L,LLOQ为0.02ng/m L。首次进行注射用1的人体药代动力学研究,经验证,符合人体药动学研究要求。5、10、20μg3个剂量组单次给药的主要药动学参数分别为cmax(0.1292±0.0419)、(0.2537±0.0369)、(0.5308±0.1626)ng/m L;tmax(0.321±0.144)、(0.510±0.313)、(0.541±0.275)h;t1/2(6.589±2.018)、(7.047±2.560)、(6.956±3.225)h,为注射用1的开发和临床应用提供了参考。A LC-MS/MS method was established to determine the tetrodotoxin(1)in human plasma.The Waters Atlantis HILIC Silica chromatography column(2.1 mmx100 mm,3μm)was used,with the mobile phase of acetonitrile-water-acetic acid.The flow rate was 0.40 mL/min,the column temperature was 40 C,and the injection volume was 10μL.The linear range of this method was 0.02-5 ng/mL,and the LLOQ was 0.02 ng/mL.The human pharmacokinetic study of 1 injection was conducted for the first time,and the results were validated to meet the requirements of human pharmacokinetic research.The main pharmacokinetic parameters for a single dose of 3 dose groups(5,10,and 20μg)were as follows:the Cmx of(0.1292±0.0419),(0.2537±0.0369)and(0.5308±0.1626)ng/mL,the tmax of(0.321±0.144),(0.510±0.313)and(0.541±0.275)h,and the tu/2 of(6.589±2.018),(7.047±2.560)and(6.956±3.225)h,respectively,which provided a reference for the development and clinical application of 1 injection.

关 键 词：替曲朵辛 液质联用 固相萃取 药代动力学 

分 类 号：R917[医药卫生—药物分析学]