摘要
目的建立了测定肾功能亢进(ARC)患者血浆中亚胺培南(IMP)浓度的超高效液相色谱-串联质谱(UPLC-MS/MS)方法,并研究IMP在ARC患者体内的药代动力学特征。方法血浆样品用乙腈沉淀蛋白处理,以阿莫西林为内标,采用UPLC-MS/MS法分析。筛选IMP的给药方案为1 g,静脉滴注,每隔8 h的ARC患者,收集不同时间点的血药浓度,计算药代动力学参数。结果IMP在0.40~200.00μg/mL范围内线性良好,精密度、准确度、基质效应、方法回收率和稳定性均符合要求。IMP在ARC患者体内的半衰期为(0.97±0.06)h,血药浓度-时间曲线下面积(AUC)为(48.49±14.93)mg/(L·h),表观分布容积为(16.15±7.90)L,肌酐清除率为(18.30±5.70)L/h,达峰浓度为(15.63±4.60)μg/mL。结论UPLC-MS/MS法准确度高、灵敏度强,可有效用于测定ARC患者血浆中IMP浓度。ARC患者体内IMP的代谢速率和清除率可能发生变化,为临床用药提供重要参考。
Objective To establish a ultra performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)assay to quantify plasma imipenem(IMP)in patients with Augmented Renal Clearance(ARC),and to investigate the pharmacokinetic characteristics of IMP in patients with ARC.Methods The plasma samples were treated with acetonitrile precipitated protein and analyzed by UPLC-MS/MS method with amoxicillin as the internal standard.ARC patients with IMP administration regimen of 1 g,intravenous drip,ARC patients at an interval of 8 h were screened,blood samples were collected at different times and plasma concentrations were detected,and pharmacokinetic parameters were calculated.Results Linear calibration curves of IMP were generated over the range of 0.40-200.00μg/mL,and the precision,accuracy,matrix effect,method recovery and stabilityall met the requirements.The half-life of IMP in ARC patients was(0.97±0.06)h,the area under the drug curve(AUC)was(48.49±14.93)mg/(L·h),the apparent volume of distribution was(16.15±7.90)L,and the creatinine clearance rate was(18.30±5.70)L/h.The peak concentration was(15.63±4.60)μg/mL.Conclusion This method has high accuracy and high sensitivity,and can be effectively applied to the detection of IMP concentration in plasma of ARC patients.The metabolic rate and clearance rate of IMP may change in ARC patients,which provides an important reference for clinical drug use.
作者
何瑶
李福书
余志杰
陈肖
HE Yao;LI Fushu;YU Zhijie;CHEN Xiao(Department of Pharmacy,Chongqing Emergency Medical Center,Chongqing 400014,China)
出处
《现代医药卫生》
2024年第19期3259-3263,共5页
Journal of Modern Medicine & Health
基金
重庆市科卫联合医学科研项目(2023MSXM090)
重庆市临床药学重点专科建设项目(渝卫办发〔2023〕2号)。
关键词
亚胺培南
肾功能亢进
治疗药物浓度监测
液相色谱串联质谱
药代动力学
Imipenem
Augmented renal clearance
Therapeutic drug monitoring
Ultra performance liquid chromatography-tandem mass spectrometry
Pharmacokinetics
