首页|基于LC-MS/MS的头孢他啶-阿维巴坦钠的血药浓度测定研究

基于LC-MS/MS的头孢他啶-阿维巴坦钠的血药浓度测定研究

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目的:建立基于液相色谱串联质谱法(liquid chromatography-tandem mass spectrometry,LC-MS/MS)的头孢他啶-阿维巴坦钠的血药浓度测定方法,为临床头孢他啶-阿维巴坦钠的安全、合理用药提供参考。方法:以ACQUITY UPLC BEH C18 色谱柱(2。1 mm×50 mm,1。7 μm)、10 mmol/L乙酸铵(A)-100%乙腈(B)流动相、0。3 mL/min流速、正负离子切换多反应监测模式等为条件,建立LC-MS/MS的头孢他啶-阿维巴坦钠的血药浓度测定方法,并检验该测定方法的专属性、精密度、准确度、回收率、稳定性。结果:头孢他啶和阿维巴坦的保留时间分别为0。89 min和 0。46 min,血浆中内源性物质对头孢他啶和阿维巴坦的检测无过多干扰;头孢他啶的线性方程为y=537。989x+56。449 6(r=0。995 3),其在 0。5~200 μg/mL浓度范围内具有较好的线性表现;阿维巴坦的线性方程为y=1 788。74x+25。226 9(r=0。998 0),其在 0。05~25 μg/mL浓度范围内具有较好的线性表现;高、中、低浓度的头孢他啶和阿维巴坦样品的批内、批间精密度均在 15。00%以内,而其准确度则均在±15。00%之间;而该方法中头孢他啶和阿维巴坦的回收率均在 80。00%以上;此外,在样品在室温下放置 6h、在进样盘中放置 24 h、在 4℃下放置24h和反复冻融(-80℃→25℃)3次等情况下,高、中、低浓度的头孢他啶和阿维巴坦样品的测量偏差均在±15。00%之间。结论:该方法具有较好的专属性和较大的线性范围,并且精密度、准确度、稳定性均较好,可以为临床患者头孢他啶-阿维巴坦钠的个体化用药提供依据。
Study on Determination of Plasma Concentration of Ceftazidime-Avibactam Sodium by LC-MS/MS
Objective:To establish a method for determination of plasma concentration of ceftazidime-avibactam sodium by liquid chromatography-tandem mass spectrometry(LC-MS/MS),and provide a reference for the safe and rational use of ceftazidime-avibactam sodium in clinical practice.Methods:A method for determination of plasma concentration of ceftazidime-avibactam sodium by LC-MS/MS was established by using an ACQUITY UPLC BEH C18 column(2.1 mm×50 mm,1.7 μm),10 mmol/L ammonium acetate(A)-100%acetonitrile(B)as a mobile phase,a flow rate of 0.3 mL/min,and a positive/negative ionization switching multiple reaction monitoring(MRM)mode,etc.,and the specificity,precision,accuracy,recovery,stability of the method were tested.Results:The retention times of ceftazidime and avibactam were 0.89 min and 0.46 min,respectively.Endogenous substances in plasma had no interference with the detection of ceftazidime and avibactam.The linear equation of ceftazidime was y=537.989x+56.449 6(r=0.995 3),with good linear performance within the concentration range of 0.5-200μg/mL;the linear equation of avibactam was y=1 788.74x+25.226 9(r=0.998 0),with good linear performance within the concentration range of 0.05-25μg/mL.The intra-batch and inter-batch precisions of high-,medium-and low-concentration ceftazidime and avibactam samples were all within 15.00%,and their accuracy was within±15.00%.The recoveries of ceftazidime and avibactam in this method were above 80.00%.In addition,when the samples were stored at room temperature for 6 h,stored in the sample injection tray for 24 h,stored at 4℃for 24 h and repeatedly frozen and thawed(-80℃→25℃)for 3 cycles,the measurement deviations of high-,medium-and low-concentration ceftazidime and avibactam samples were all within±15.00%.Conclusion:This method has good specificity and a large linear range,and has good precision,accuracy and stability,which can provide a basis for the individualized medication of ceftazidime-avibactam sodium in clinical patients.

ceftazidime-avibactam sodiumplasma concentrationliquid chromatography-tandem mass spectrometry(LC-MS/MS)

王银辉、张小丽、范炜斌、杨利婷、林彬

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长兴县人民医院,浙江 湖州 313100

湖州市智能药学与个体化治疗重点实验室,浙江 湖州 313100

温州医科大学仁济学院,浙江 温州 325000

头孢他啶-阿维巴坦钠 血药浓度 液相色谱串联质谱法(LC-MS/MS)

浙江省药学会医院药学专项科研资助项目2022年浙江省医学会临床医学科研专项资金项目

2019ZYY472022ZYC-Z34

2024

抗感染药学
江苏省苏州市第五人民医院

抗感染药学

影响因子:0.505
ISSN:1672-7878
年,卷(期):2024.21(7)