人血浆中安罗替尼质量浓度测定方法的建立及其应用
x

请在关注微信后,向客服人员索取文件

篇名: 人血浆中安罗替尼质量浓度测定方法的建立及其应用
TITLE: Establishment and Application of Method for Concentration Determination of Anlotinib in Human Plasma
摘要: 目的:建立测定人血浆中安罗替尼质量浓度的方法并应用于临床。方法:以醋酸铵为盐析助剂,以乙腈为溶剂,采用盐析辅助液液萃取对血浆样品进行前处理;以伏立康唑为内标,采用液相色谱-串联质谱法(LC-MS/MS)测定。色谱柱为WatersXBridgeC18,流动相为0.2%甲酸水溶液-乙腈(梯度洗脱),流速为1mL/min,柱温为40℃,进样量为10μL,分流比为3∶7;离子源为电喷雾离子源,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/z408.3→339.3(安罗替尼)、m/z350.2→281.3(内标)。结果:安罗替尼检测质量浓度的线性范围为0.2~200ng/mL(R2=0.9967);定量下限为0.2ng/mL;日内、日间精密度试验的RSD均小于12%(n=6或n=3);准确度为90.92%~108.00%(n=6或n=3);平均提取回收率为87.51%~100.00%(RSD<8%,n=6);平均基质效应为96.66%~99.93%(RSD<5%,n=6)。3例使用安罗替尼治疗的非小细胞肺癌患者体内的血药浓度为8.74~65.60ng/mL。结论:该方法操作简单、准确度高、专属性强,可用于非小细胞癌患者体内安罗替尼的血药浓度监测。
ABSTRACT: OBJECTIVE:To establish a method for concentration determination of anlotinib in human plasma and apply it in the clinic. METHODS :The plasma samples were pretreated by salting-out assisted with liquid-liquid extraction with ammonium acetate as salting out assistant and acetonitrile as solvent. Using voriconazole as internal standard ,LC-MS/MS method was adopted. The separation was performed on Waters X Bridge C 18 column with mobile phase consisting of 0.2% formic acid solution- acetonitrile(gradient elution )at the flow rate of 1 mL/min. The column temperature was set at 40 ℃,and sample size was 10 μL. The split ratio was 3∶7. The electrospray ion source and multiple reaction monitoring mode were used for the analysis. The ion pair of anlotinib and internal standard under positive ion mode were m/z 408.3→339.3 and m/z 350.2→281.3,respectively. RESULTS : Anlotinib showed a good linear relationship in the concentration range of 0.2-200 ng/mL(R2>0.996 7). The lowest limit of quantitation was 0.2 ng/mL. Intra-day and inter-day RSDs were no more than 12% (n=6 or n=3). Accuracies were 90.92%-108.00%(n=6 or n=3). The average extraction recoveries were 87.51%-100.00%(RSD<8%,n=6). The average matrix effects were 96.66%-99.93%(RSD<5%,n=6). The plasma concentration of 3 patients with NSCLC treated with anlotinib was 8.74-65.60 ng/mL. CONCLUSIONS :The method is simple ,accurate and specific ,and is suitable for the plasma concentration monitoring of anlotinib in NSCLC patients.
期刊: 2021年第32卷第11期
作者: 周利娟,武正华,汪硕闻,缪文清,包婺平,包爱华,范国荣
AUTHORS: ZHOU Lijuan ,WU Zhenghua ,WANG Shuowen ,MIAO Wenqing ,BAO Wuping ,BAO Aihua,FAN Guorong
关键字: 安罗替尼;液相色谱-串联质谱技术;盐析辅助液液萃取;治疗药物监测
KEYWORDS: Anlotinib;LC-MS/MS;Salting-out assisted liquid-liquid extraction ;Therapeutic drug monitoring
阅读数: 402 次
本月下载数: 5 次

* 注:未经本站明确许可,任何网站不得非法盗链资源下载连接及抄袭本站原创内容资源!在此感谢您的支持与合作!