HPLC法测定连续性肾脏替代治疗脓毒血症患者的哌拉西林/他唑巴坦血药浓度及临床应用
Simultaneous determination of serum concentration of piperacillin/tazobactam in patients receiving continuous renal replacement therapy treatment by HPLC and its clinical application
何玲芳 1王直滔 2楼永海 2徐庆圣3
作者信息
- 1. 浙江省临海市中医院康复科,台州 317000
- 2. 浙江省台州医院药剂科,台州 317099
- 3. 温州医科大学药学院,温州 325035
- 折叠
摘要
目的 建立HPLC法测定连续性肾脏替代治疗(CRRT)脓毒血症患者哌拉西林/他唑巴坦的血药浓度,以指导临床个体化用药方案设计.方法 选用流动相为0.1 mol·L-1的磷酸二氢钠溶液(A)-乙腈(B),采用梯度洗脱的方法对乙腈进行处理,流速为1 mL·min-1,柱温为30℃,检测波长为220 nm,pH值为6.4,进样量为20 μL,建立测定CRRT的脓毒血症患者哌拉西林/他唑巴坦血药浓度的HPLC法.采用该方法测定12例CRRT的脓毒血症患者哌拉西林/他唑巴坦血药浓度达到稳态时的谷浓度.结果 在5～300 mg·L-1的范围内哌拉西林质量浓度与峰面积具有线性关系(Y=0.134 6X-0.0612,r=0.999 3).在1～50mg·L-1的范围内他唑巴坦质量浓度与峰面积具有线性关系(Y=0.060 7X+0.068 7,r=0.999 2).哌拉西林和他唑巴坦的平均回收率分别为99.19％和100.13％,日内和日间精密度均小于8％.12例CRRT的脓毒血症患者哌拉西林血药浓度均高于最低抑菌浓度(4 mg·L1),但其中有2例低于最低抑菌浓度的4倍,他唑巴坦的血药浓度均高于最低抑菌浓度(1 mg·L-1).结论 该研究建立的HPLC法测定哌拉西林/他唑巴坦血药浓度的方法操作简便,检测成本低,能满足临床血药浓度监测需求,适合基层医疗机构进行个体化给药方案设计时使用.
Abstract
AIM To establish a high-performance liquid chromatography(HPLC)method for simultaneous determination of piperacillin/tazobactam concentrations in the serum of patients receiving continuous renal replacement therapy(CRRT)treatment,so as to apply them to clinical practice for personalized drug design.METHODS The mobile phase was a mixture of acetonitrile and 0.1 mol·L-1 sodium dihydrogen phosphate solution.Acetonitrile was treated by gradient elution at a flow rate of 1 mL·min-1.The flow rate was 1 mL·min-1,the column temperature was 30℃,the detection wavelength was 220 nm,the pH value was 6.4,and the injection amount was 20 µL.The HPLC method was established to determine piperacillin/tazobactam concentration in patients receiving continuous renal replacement therapy treatment.The trough concentration of piperacillin/tazobactam in the serum of 12 sepsis patients with CRRT was determined by the method when the blood concentration reached a steady state.RESULTS There was a linear relationship between concentration range of 5-300 mg·L-1 and peak area for piperacillin(Y=0.134 6X-0.061 2,r=0.999 3).A linear relationship was obtained between concentration range of 1-50 mg·L-1and peak area for tazobactam(Y=0.060 7X+0.068 7,r=0.999 2).Average recoveries of piperacillin and tazobactam were 99.19％and 100.13％,respectively,with intra-day and inter-day precision less than 8％.The serum drug concentrations of piperacillin in 12 patients were all higher than the minimum inhibitory concentration(4 mg·L-1),but serum drug concentrations in 2 cases were below 4 times the minimum inhibitory concentration.The serum concentration of tazobactam was higher than 1 mg·L-1.CONCLUSION The HPLC method for detecting the serum concentration of piperacillin/tazobactam is simple to operate,with low instrument and detection costs,and can meet the needs of clinical practice testing.It is more suitable for adjusting personalized medication plans in primary medical institutions.
关键词
哌拉西林/他唑巴坦/HPLC/血药浓度/治疗药物监测Key words
piperacillin/tazobactam/high-performance liquid chromatography/therapeutic drug monitoring引用本文复制引用
基金项目
浙江省药学会医院药学专项科研资助项目(2017ZYY27)
出版年
2024
国家科技期刊平台
NSTL
万方数据