摘要
目的建立准确、灵敏的高效液相色谱-质谱联用法(high performance liquid chromatography-mass spectrometry,HPLC-MS/MS)测定持续肾脏替代(continuous renal replacement, CRRT)时人血浆中哌拉西林钠/他唑巴坦钠的浓度。方法选用高、低两种剂量给药,采取单制剂双周期序贯试验设计,对12例行CRRT患者完成哌拉西林/他唑巴坦钠静脉滴注之后,使用HPLC-MS/MS方法同时测定哌拉西林及他唑巴坦的浓度。采用Gemini C18(50mm×3.0 mm,3μm)分析柱;流动相为甲醇:乙腈:水:1 mol/L氨水:甲酸(25∶15∶60∶0.1∶0.05),质谱检测采用电喷雾离子源,多反应离子监测(MRM)模式检测。结果血浆中哌拉西林线性范围为1~100 mg/L,他唑巴坦线性范围为0.5~40.0 mg/L,高、中、低3个浓度日内及日间精密度均小于5%。实测12例行CRRT患者,血药浓度与给药剂量呈相关性。结论高效液相色谱-质谱联用法灵敏度高、特异性好,可以运用于脓毒症患者接受CRRT时血浆哌拉西林/他唑巴坦浓度的测定。
Objective To establish an accurate and sensitive high performance liquid chromatography-mass spectrometry(HPLC-MS/MS) for the determination of piperacillin in human plasma the concentration of sodium/tazobactam sodium during continuous renal replacement(CRRT). Methods The high-dose and low-dose two-dose method were used to design a single-dose two-cycle sequential test. After 12 patients with CRRT were treated with piperacillin/tazobactam sodium intravenously, HPLC-MS/MS was used simultaneously to determine the concentrations of piperacillin and tazobactam. The Gemini C18(50 mm×3.0 mm, 3 μm) analytical column was used. The mobile phase was methanol, acetonitrile, water, 1 mol/L ammonia, formic acid(25∶15∶60∶0.1∶0.05). Mass spectrometry was detected using an electrospray ion source and multiple reactive ion monitoring(MRM) mode. Results The linear range of piperacillin in plasma was 1-100 mg/L, and the linear range of tazobactam was 0.5~40.0 mg/L. The intra-day and inter-day precision of high, medium and low concentrations were less than 5%. The blood concentration of 12 patients who underwent CRRT was correlated with the dose. Conclusion High performance liquid chromatography-mass spectrometry has high sensitivity and specificity, and can be used to determine the plasma concentration of piperacillin/tazobactam in patients with sepsis receiving CRRT.
引文
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