为了研究二代头孢类新药头孢呋辛赖氨酸在肝损伤大鼠体内的药代动力学过程,建立了采用超快速液相色谱-串联质谱(UFLC-MS/MS)快速测定肝损伤模型大鼠血浆中头孢呋辛含量的方法.血浆样品在酸性条件下用乙腈沉淀蛋白,采用Shim-pack XR-ODS色谱柱(75mm×3.0mm,2.2μm)为分析柱、乙腈-0.1％甲酸水溶液(40∶60,v/v)为流动相、流速为400μL/min进行色谱分离,采用电喷雾负离子(ESI)模式电离、多反应监测(MRM)模式进行质谱检测,用于定量分析的离子对分别为m/z 423.2→206.8(头孢呋辛)和m/z 454.1→238.4(内标头孢噻肟).结果表明,大鼠血浆中头孢呋辛的质量浓度在0.01～1 mg/L和1～400 mg/L范围内线性关系良好(r＞0.99),定量限为0.01 mg/L,日内和日间精密度(以相对标准偏差(RSD)计)均小于11.5％,准确度(RE)为-7.1％～2.2％,平均萃取回收率大于83.5％,样品运行时间仅为3.0 min,能够满足生物样品的测定需求.该法简便、快速,已用于肝损伤大鼠静脉注射头孢呋辛赖氨酸的药代动力学预实验研究.%In order to investigate the pharmacokinetic profiles of cefuroxime lysine, a new second generation cephalosporins, in liver-injured rat model, an ultra fast liquid chromatography-tandem mass spectrometry (UFLC-MS/MS) method for the determination of cefuroxime in liver-injured rat plasma was developed and validated. The plasma sample was pretreated by protein precipitation with acidified acetonitrile. The analytes were separated on a Shim-pack XR-ODS column (75 mm x3. 0 mm, 2. 2 (xm) with acetonitrile-O. 1% formic acid aqueous solution (40-60, v/v) as the mobile phase at a flow rate of 400μL/min. The mass spectrometer was operated in multiple reaction monitoring (MRM) mode with a negative electrospray ionization ( ESI) interface. The precursor to product ion transitions of m/z 423. 2→206. 8 and m/z 454. 1 →238.4 were selected to determine cefuroxime and cefotaxime (internal standard, IS), respectively. The linearities ranged from 0. 01 to 1 mg/L and 1 to 400 mg/L ( r > 0. 99), and the limit of quantification of cefuroxime was 0. 01 mg/L. The relative standard deviations ( RSDs) of intra- and inter-day precisions were both less than 11.5%, and the accuracy (relative error) was between -7.1% and 2. 2%. The mean extraction recovery was more than 83. 5%. The total run time was 3.0 min per sample. The method is simple and fast for the preliminary pharmaco-kinetic study of cefuroxime lysine in liver-injured rats.
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