LC-MS/MS法快速测定人血浆中达托霉素浓度  

Quick LC-MS/MS method for the determination of daptomycin in human plasma

作　　者：肖昌钱[1] 项迎春[1] 韩奇[1] 李力[1] XIAO Chang - qian XIANG Ying - chun HAN Qi LI Li(Department of Pharmacy, Zhejiang Hospital, Hangzhou 310013, China)

机构地区：[1]浙江医院药剂科,杭州310013

出　　处：《中国临床药理学杂志》2017年第12期1149-1151,1164,共4页The Chinese Journal of Clinical Pharmacology

基　　金：国家科技重大专项项目-老年病新药临床技术平台基金资助项目(2013ZX09303005);浙江省自然科学基金资助项目(LQ15H310003);浙江省老年医学重点实验室开放基金资助项目(2014-01)

摘　　要：目的建立高效液相色谱质谱联用法(LC-MS/MS)测定人血浆中达托霉素的浓度。方法人血浆样品用乙腈沉淀蛋白后,选用Eclipse Plus C18(2.1 mm×100 mm,3.5μm)色谱柱,以乙腈-10 mmol·L^(-1)醋酸铵溶液(均含0.1%甲酸)80∶20为流动相,流速为0.25 mL·min^(-1),柱温为25℃,用电喷雾离子化源,正离子方式,多反应监测(MRM)扫描方式进行监测,用于定量分析的离子反应分别为m/z 811.0→m/z 159.1(达托霉素)和m/z 237.1→m/z 194.1(内标卡马西平),考察其专属性、标准曲线与定量下限、精密度与回收率、基质效应和稳定性。结果血浆中达托霉素的标准曲线方程为y=1.49×10^(-2)x-2.06×10^(-3)(r=0.9980),在0.10~100μg·mL^(-1)范围内线性关系良好,定量下限为0.10μg·mL^(-1);质控样品的准确度在97.1%~104.8%;日内、日间RSD均小于15%;提取回收率81.9%~91.4%。基质效应为90.1%~109.3%。结论该方法快速、灵敏、准确,专属性强,重复性好,适用于人血浆中达托霉素浓度的测定,可应用于达托霉素的血药浓度检测和药代动力学研究。Objective To develop a LC-MS/MS method for determination of daptomycinin human plasma. Methods The plasma samples were precipitated by acetonitrile,then the supernatant were separated on Eclipse Plus C18column（2. 1 mm × 100 mm,3. 5 μm） and eluted with acetonitrile-10 mmol · L^-1ammonium acetate（80 ∶ 20,containing0. 1% formic acid）,and the column temperature was 25 ℃. Detection of the analyte was achieved using positive ion electrospray ionization（ESI）in the multiple reaction monitoring（MRM） mode. The MS/MS ion transitions monitored were m/z 811. 0 → m/z 159. 1 and m/z 237. 1 → m/z194. 1 for daptomycin and internal standard,respectively. The specificity,standard curve and lower limitation of quantitation,precision and recovery rate and stability as well as the matrix effect were investigated. Results The linear regression equation was y = 1. 49 × 10^-2x-2. 06 × 10^-3（r = 0. 9980） The linear range of daptomycin was0. 10-100 μg · mL^-1,with the lower limit of quantitation（LLOQ） of0. 10 μg·mL^-1. Accuracy was 97. 1%-104. 8%,Intra-day and inter-dayrelative standard deviations were both below 15%. The absolute recovery in plasma was81. 9%-91. 4%. The matrix effects were90. 01%-109. 28%. Conclusion The established method israpid,sensitive,accurate,specific and reliable,and suitable for the determination ofdaptomycin in human plasma and pharmacokinetic study.

关 键 词：达托霉素 液质联用法 血药浓度 药代动力学 

分 类 号：R972[医药卫生—药品]