论文部分内容阅读
目的:建立灵敏、专属的液相色谱-串联质谱法同时测定人血浆中头孢他啶和他唑巴坦,并用于临床药代动力学研究。方法:血浆样品经乙腈沉淀蛋白后,以乙腈-5 mmol.L-1醋酸铵-甲酸(20∶80∶0.16,v/v/v)为流动相,使用VenusilASB-C18柱(150 mm×4.6 mm,5μm)分离。采用电喷雾电离源,多反应监测模式(MRM),以正负离子切换同时测定头孢他啶和他唑巴坦,切换时间在进样后3.8 min。头孢他啶采用正离子检测,用于定量的离子反应分别为m/z 547→468(头孢他啶),m/z 364→208(内标头孢羟氨苄),头孢他啶和内标头孢羟氨苄的保留时间分别为3.0 min和2.8 min;他唑巴坦采用负离子检测,用于定量的离子反应分别为m/z 299→138(他唑巴坦),m/z 232→140(内标舒巴坦),他唑巴坦和内标舒巴坦的保留时间分别为4.4 min和4.9 min。结果:头孢他啶和他唑巴坦的线性范围分别为0.250～250μg.mL-1和0.0250～25.0μg.mL-1,日内、日间精密度(RSD)均小于10.8%,准确度(RE)在-7.6%～2.1%之间。本法被成功应用于健康受试者静脉滴注不同剂量头孢他啶/他唑巴坦钠(6∶1)注射液(头孢他啶/他唑巴坦含量分别为1 g/0.167 g,2 g/0.333 g,4 g/0.667 g)的药动学研究。结论:该方法专属性强,灵敏度高,操作简便,适用于注射用头孢他啶/他唑巴坦临床药代动力学研究。
OBJECTIVE: To develop a sensitive and specific liquid chromatography-tandem mass spectrometry for the simultaneous determination of ceftazidime and tazobactam in human plasma and to study its pharmacokinetics in clinical practice. Methods: After the plasma samples were separated by acetonitrile precipitation, the mobile phase was acetonitrile-5 mmol·L-1 ammonium acetate-formic acid (20:80:0.16, v / v / v) mm, 5 μm). Electrospray ionization source and multi-reaction monitoring mode (MRM) were used to determine ceftazidime and tazobactam simultaneously with positive and negative ion switching. The switching time was 3.8 min after injection. Ceftazidime was detected by positive ion. The ion reactions for quantification were m / z 547 → 468 (ceftazidime), m / z 364 → 208 (internal standard cefadroxil), and the retention times of ceftazidime and cefadroxil were 3.0 min and 2.8 min respectively. Tazobactam was detected by negative ions and the quantitative ion reaction was m / z 299 → 138 (tazobactam), m / z 232 → 140 The retention times of zolbactan and internal standard sulbactam were 4.4 min and 4.9 min, respectively. Results: The linear range of ceftazidime and tazobactam was 0.250 ~ 250μg.mL-1 and 0.0250 ~ 25.0μg.mL-1 respectively. The intra-day and inter-day precision was less than 10.8%, and the accuracy was -7.6% ~ 2.1%. This method has been successfully applied to healthy subjects intravenous infusion of different doses of ceftazidime / tazobactam sodium (6: 1) injection (ceftazidime / tazobactam levels were 1 g / 0.167 g, 2 g / 0.333 g , 4 g / 0.667 g) pharmacokinetic study. Conclusion: This method is specific, sensitive and easy to operate. It is suitable for clinical pharmacokinetics of ceftazidime / tazobactam for injection.