LC-MS/MS法同时测定耐碳青霉烯肠杆菌感染重症患者血浆中替加环素及阿米卡星的药物浓度  

Simultaneous determination of tegacyclin and amikacin in severe patients plasma with carbapenem resistant enterobacter infection by LC-MS/MS

作　　者：饶志[1] 郭思鸣 何忠芳[1] 党子龙[1] 李波霞[1] 秦红岩[1] 魏玉辉[1] RAO Zhi;GUO Si-ming;HE Zhong-fang;DANG Zi-long;LI Bo-xia;QIN Hong-yan;WEI Yu-hui(Department of Pharmacy,the First Hospital of Lanzhou University,Lanzhou 730000,China;School of Pharmacy,Lanzhou University,Lanzhou 730000,China)

机构地区：[1]兰州大学第一医院药剂科,兰州730000 [2]兰州大学药学院,兰州730000

出　　处：《药物分析杂志》2023年第3期387-393,共7页Chinese Journal of Pharmaceutical Analysis

基　　金：甘肃省自然科学基金(21JR7RA353,21JR7RA370,21JR7RA380);兰州大学第一医院院内基金(ldyyyn2018-31)。

摘　　要：目的:建立同时测定重症加强护理病房(ICU)中耐碳青霉烯肠杆菌(CRE)感染患者替加环素及阿米卡星的血浆药物浓度的液相色谱-串联质谱(LC-MS/MS)方法,并将其应用于治疗药物监测(TDM)中。方法:血浆样品加入内标米诺环素及卡那霉素的甲醇溶液及氢氧化钠溶液,采用乙酸乙酯与二氯甲烷混合溶液提取,取上清液氮气吹干,加入甲醇复溶后进样分析。采用Waters Cortecs C18(100 mm×4.6 mm, 2.7μm)色谱柱,流动相A为甲醇,流动相B为甲酸-甲酸铵水溶液,流速0.3 mL·min-1,进样量2μL。检测以电喷雾离子源,正离子扫描,多反应监测模式进行。结果:替加环素及阿米卡星在ICU患者血浆中的线性范围及定量限均符合测定要求,批内、批间精密度、提取回收率、基质效应及稳定性均<15%。收集到10例同时接受替加环素(50 mg,每12 h服用1次)和阿米卡星(0.8 g,每天服用1次)治疗的CRE感染重症患者样本,2种药物血浆中稳态谷浓度分别为(88.45±98.97)ng·mL^(-1)及(2.98±1.59)μg·mL^(-1),存在较大个体差异。结论:本方法快速、灵敏,专属性强且重复性好,可进行CRE感染的ICU患者临床TDM工作。Objective:To develop a method for simultaneous determination of the plasma drug concentrations of tegacyclin and amikacin in infection in intensive care unit(ICU)patients with carbapenem resistant enterobacteri-aceae(CRE)using LC-MS/MS,and apply it to the therapeutic drug monitoring(TDM).Methods:NaOH so-lution and methanol solution with internal standards of minocycline and kanamycin were added into plasma samples.The resulting solution was then extracted with the mixed solution of ethyl acetate and methylene chloride.The supernatant was dried with nitrogen and re-dissolved in methanol.Determination was carried out with a waters Cortec C18(100 mm×4.6 mm,2.7μm)chromatographic column.Mobile phase A was methanol,mobile phase B was formic acid/ammonium formate aqueous solution,the flow rate was 0.3 m L·min-1,and the injec-tion volume was 2μL.Electrospray spray ion source,positive ion scanning and multiple reaction monitoring mode were used.Results:The linear range and quantitative limit of tegacyclin and amikacin both met the requirements.The inter-and intra-day precision and matrix effect were all<15%.Samples of ten patients treated with tega-cyclin(50 mg,q12 h)and amikacin(0.8 g,qd)were collected.The steady-state trough concentrations of tegacyclin and amikacin in ten ICU patients with CRE infection were(83.86±84.56)ng·mL^(-1) and(83.86±84.56)ng·mL^(-1),respectively.There were large individual differences caused by the two antibiotics.Conclusion:This method is rapid,sensitive,specific and reproducible.It can be used for clinical TDM of ICU patients with CRE infection.

关 键 词：液相色谱质谱联用法 耐碳青霉烯肠杆菌 重症患者 替加环素 阿米卡星 治疗药物监测 

分 类 号：R917[医药卫生—药物分析学]