论文部分内容阅读
目的:建立人血浆中磷霉素的高效液相色谱-串联质谱测定方法。方法:50μL血浆中加入50μL内标溶液(福多司坦),250μL甲醇,漩涡混匀;离心取30μL上清液,与100μL注射用水混匀,取20μL进行LC-MS/MS分析。采用UltramateTM XB-CN分析柱(150mm×4.6mm,5μm),以甲醇-5mmol.L-1醋酸铵溶液(10∶90)为流动相,流速0.7mL.min-1,柱温22℃,进样量20μL。采用API4000型三重四极杆串联质谱仪,负离子方式检测;扫描方式为多反应监测,用于定量分析的离子反应分别为m/z137→m/z79(磷霉素)和m/z178→m/z91(福多司坦)。结果:血浆中磷霉素在0.10～12.0mg.L-1范围内线性关系良好(r=0.996 3),最低检测限为0.10mg.L-1。该方法的日内和日间精密度均小于10.6%。血浆中低、中、高3种浓度的绝对回收率(n=5)分别为95.4%,95.9%,91.6%。结论:本研究中的检测方法操作简单,灵敏,准确,重复性好,适用于该药的临床药动学研究。
Objective: To establish a method for the determination of fosfomycin in human plasma by high performance liquid chromatography-tandem mass spectrometry. Methods: 50μL internal standard solution (furadosteine) was added to 50μL plasma and mixed with vortex with 250μL methanol. The supernatant was centrifuged and mixed with 100μL water for injection. 20μL was taken for LC-MS / MS analysis. UltramateTM XB-CN analytical column (150mm × 4.6mm, 5μm) was used with mobile phase of methanol-5mmol.L-1 ammonium acetate (10:90) as mobile phase at a flow rate of 0.7mL · min- Sample volume 20μL. The triple quadrupole tandem mass spectrometer (API4000) was used for negative ion detection. The scanning mode was multi-reaction monitoring. The ion reactions for quantitative analysis were m / z137 → m / z79 (fosfomycin) and m / z178 → m / z91 (fodostan). Results: There was a good linear relationship between fosfomycin in the range of 0.10-12.0 mg.L-1 (r = 0.996 3) and the lowest limit of detection was 0.10 mg.L-1. The precision of the method was less than 10.6% during the day and the day. The absolute recoveries (n = 5) of plasma at low, medium and high concentrations were 95.4%, 95.9% and 91.6%, respectively. Conclusion: The detection method in this study is simple, sensitive, accurate and reproducible. It is suitable for clinical pharmacokinetic study of this drug.