LC-MS/MS法测定人血浆中吡嗪酰胺的药物浓度  

Determination of the Concentration of Pyrazinamide in Human Plasma by LC-MS/MS

作　　者：潘碧妍 陈禧翎 周小琴 陈红英 Pan Biyan;Chen Xiling;Zhou Xiaoqin;Chen Hongying(Guangzhou Baiyunshan Mingxing Pharmaceutical Co.,Ltd.,Guangzhou 510250,China)

机构地区：[1]广州白云山明兴制药有限公司,广东广州510250

出　　处：《广东化工》2024年第23期133-135,共3页Guangdong Chemical Industry

基　　金：广州市产学研协同创新重大专项(201604046024)。

摘　　要：目的:建立测定人血浆中吡嗪酰胺药物浓度的方法。方法:以吡嗪酰胺-d3为内标,血浆样品经蛋白沉淀后,采用液相色谱-串联质谱法测定吡嗪酰胺的质量浓度。以AQUASIL C_(18)为色谱柱,流动相A为水溶液,流动相B为95%乙腈溶液,两相均含0.1%甲酸和2 mmol·L^(-1)醋酸铵,采用溶剂梯度结合流速梯度的洗脱方式,柱温40℃,进样量10μL;采用电喷雾离子源,以多反应监测模式进行正离子扫描,用于定量分析的离子对分别为m/z 124.10→81.10(吡嗪酰胺)、m/z 127.10→84.10(内标)。结果:吡嗪酰胺检测质量浓度的线性范围为40 ng·mL^(-1)~20000 ng·mL^(-1)(R2>0.9992),定量下限为40 ng·mL^(-1);批内、批间精密度,准确度,提取回收率,基质效应,稳定性均符合相关要求。结论:所建LC-MS/MS法操作简便、快速,可用于吡嗪酰胺的临床药代动力学研究。Objective:To establish a method for determining the concentration of pyrazinamide in human plasma.Methods:Using pyrazinamide-d3 as internal standard,the plasma concentrations of pyrazinamide were determined by LC-MS/MS after protein precipitation.The liquid chromatographic separation process was performed on an AQUASIL C_(18) column by solvent gradient combined with velocity gradient elution.The mobile phases were consisted of water(mobile phase A)and acetonitrile-water(5∶95,V/V,mobile phase B),both contained 0.1%formic acid and 2 mmol·L^(-1) ammonium.The column temperature was set at 40℃,and an injection volume of 10μL for each sample was sufficiently detected.The electrospray ion source and multi-reaction monitoring mode were used for positive iron scanning.The ion pair used for quantitative analysis of pyrazinamide and internal standard were m/z 124.10→81.10 and m/z 127.10→84.10,respectively.Results:The linear range of pyrazinamide were 40 ng·mL^(-1)~20000 ng·mL^(-1)(R2>0.9992),and the lower limit of quantification was 40 ng·mL^(-1).The precision and accuracy within and between batches,extraction recovery rate,matrix effect and stability all met relevant requirements.Conclusion:The established method is simple,rapid and suitable for the clinical pharmacokinetic studies.

关 键 词：吡嗪酰胺 血浆药物浓度 液相色谱-串联质谱法 流速梯度 

分 类 号：R917[医药卫生—药物分析学]