丙泊酚血药浓度检测方法建立及在淋巴水肿患者中的应用  

Establishment of a method for detecting propofol concentration in plasma and its application in patients with lymphedema

作　　者：李京峰 时正媛[1] 张梦洁 关雷[2] 姜德春 LI Jingfeng;SHI Zhengyuan;ZHANG Mengjie;GUAN Lei;JIANG Dechun(Dept.of Pharmacy,Beijing Shijitan Hospital Affiliated to Capital Medical Hospital,Beijing 100038,China;Dept.of Anesthesiology,Beijing Shijitan Hospital Affiliated to Capital Medical Hospital,Beijing 100038,China)

机构地区：[1]首都医科大学附属北京世纪坛医院药剂科,北京100038 [2]首都医科大学附属北京世纪坛医院麻醉科,北京100038

出　　处：《中国药房》2024年第4期476-480,共5页China Pharmacy

基　　金：首都医科大学附属北京世纪坛医院淋巴外科开放课题。

摘　　要：目的建立测定人血浆中丙泊酚浓度的方法并应用于淋巴水肿患者血药浓度检测。方法以麝香草酚为内标,血浆样品经蛋白沉淀后,采用超高效液相色谱-串联质谱(UPLC-MS/MS)法测定丙泊酚的浓度。以Kinetex C18为色谱柱,以乙腈(A)-水(B)为流动相进行梯度洗脱,流速为200μL/min,进样量为5μL,柱温为40℃,样品仓温度为15℃。采用多反应监测模式进行检测,用于定量分析的离子对为m/z 177.0→161.2(丙泊酚)、m/z 149.0→133.1(内标)。采用上述方法测定6例淋巴水肿患者血浆中丙泊酚的血浆浓度。结果丙泊酚检测质量浓度的线性范围为50~5000 ng/mL(r=0.9950);批内、批间精密度的RSD均不高于8.08%;空白血浆中无内源性干扰;无残留效应和稀释效应;提取回收率为89.80%~93.73%,基质效应为97.93%~101.73%;稳定性试验的RSD均小于3.27%。术中靶控输注2~30 min内,6例患者的丙泊酚血药浓度为1865.3~6056.2 ng/mL,停药后4~8 h内基本代谢完全。结论所建UPLC-MS/MS法可以在不进行衍生化的前提下,实现对丙泊酚的测定,样品前处理过程简便、快速,可用于淋巴水肿患者血浆样本中丙泊酚的血药浓度检测。OBJECTIVE To establish a method for the determination of propofol concentration in human plasma and apply it in patients with lymphedema.METHODS The concentration of propofol was determined by UPLC-MS/MS after protein precipitation of plasma samples using thymol as internal standard.The sample was eluted on a Kinetex C18 column with a mobile phase consisting of acetonitrile(A)-water(B)for gradient elution at the flow rate of 200μL/min.The sample size was 5μL,and the column temperature was set at 40℃.The sample chamber temperature was 15℃.Using multi-reaction monitoring mode,the ion pairs for quantitative analysis were m/z 177.0→161.2(propofol)and m/z 149.0→133.1(internal standard),respectively.The above method was used to determine the plasma concentration of propofol in 6 patients with lymphedema.RESULTS The linear range of propofol was 50-5000 ng/mL(r=0.9950).RSDs of within-and between-batch precision were not more than 8.08%;no endogenous interference,carryover effect,or dilution effect was observed in blank plasma.The extraction recovery ranged from 89.80%to 93.73%,and matrix effects were within the range of 97.93%-101.73%.RSDs of the stability test were all lower than 3.27%.During intraoperative TCI 2-30 min,the plasma concentration of propofol in 6 patients was maintained in the range of 1865.3-6056.2 ng/mL,and the propofol was almost excreted within 4-8 h after operation.CONCLUSIONS The established UPLC-MS/MS method in this study can achieve the determination of propofol and a simple and fast sample pretreatment process without derivatization;it is proved to be suitable for the concentration monitoring of propofol in plasma samples of patients with lymphedema.

关 键 词：超高效液相-串联质谱法 丙泊酚 淋巴水肿 血药浓度 

分 类 号：R969.3[医药卫生—药理学] R917[医药卫生—药学]