液质联用在单硝酸异山梨酯生物等效性研究中的应用  

Application of LCMS in bioequivalence study of isosorbide mononitrate

作　　者：刘增花 吉健 张金玉 孟祥建 周田田 孙宏辉 Liu Zenghua;Ji Jian;Zhang Jinyu;Meng Xiangjian;Zhou Tiantian;Sun Honghui(Weifang Xingtaike Microelectronics Material Limited Company,Weifang 261041,Shandong,China;Shandong Green Testing Limited Company,Weifang 261041,Shandong,China)

机构地区：[1]潍坊星泰克微电子材料有限公司,潍坊261041 [2]山东格林检测股份有限公司,潍坊261041

出　　处：《分析仪器》2024年第6期32-37,共6页Analytical Instrumentation

摘　　要：目的:建立LC-MS/MS法为该研究提供方法学依据。方法:采用单硝酸异山梨酯同位素作为内标(5-ISMN-D6),Waters BEH C18色谱柱(2.1×100mm,1.7μm),以0.01%乙酸水和甲醇为流动相,设定流速为0.4mL/min,采用梯度洗脱法,多反应监测(MRM)负离子扫描模式,定量分析离子对为:m/z 250.00→59.00,内标离子对为:m/z 256.00→59.00,血浆样本用甲醇提取,进样量2μL,线性范围25~2000ng/mL,定量下限25ng/mL。通过对预实验药动学参数Cmax、AUC及Tmax的分析发现两种受试、参比两种制剂并无显著差异。结论:该方法选择性好、灵敏度高、稳定性好、前处理血浆用量少,适用于测定人血浆中单硝酸异山梨酯含量;其药动学研究结果表明预实验中两种制剂具有生物等效性,对临床中单硝酸异山梨酯相关疾病治疗及合理用药具有指导意义。This method provides methodological basis for pre-experimental study on bioequivalence of isosorbide mononitrate(5-ISMN).Isosorbide mononitrate was used as internal standard(5-ISMN-D6).The chromatography was performed on Waters BEH C18 column(2.1×100mm,1.7μm)with 0.01%acetic acid water and methanol as mobile phases at a flow rate of 0.4mL/min.Gradient elution method was adopted.Multiple reaction monitoring(MRM)negative ion scanning mode was selected.The quantitative analysis of ion pairs was m/z 250.00→59.00,of the internal standard ion pairs was m/z 256.00→59.00.The plasma samples were extracted with methanol,with an injection volume of 2μL.The linear range was 25-2000ng/mL,the lower limit of quantification was 25ng/mL.Through the analysis of pre-experimental pharmacokinetic parameters Cmax,AUC and Tmax,it was found that there was no significant difference between the two subjects and the two reference.The method has good selectivity,high sensitivity,good stability,and requires less amount of pre-treated plasma.The results of pharmacokinetic study show that the two preparations are bioequivalent in the preliminary experiment.

关 键 词：单硝酸异山梨酯 液质联用法 生物等效性 药代动力学 血浆 

分 类 号：O657.63[理学—分析化学] TQ460.72[理学—化学]