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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
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李京峰 ,时正媛 ,张梦洁 ,关 雷 ,姜德春 (1.首都医科大学附属北京世纪坛医院药剂科,北京 100038;
1*
1
2
2
2.首都医科大学附属北京世纪坛医院麻醉科,北京 100038)
中图分类号 R969.3;R917 文献标志码 A 文章编号 1001-0408(2024)04-0476-05
DOI 10.6039/j.issn.1001-0408.2024.04.18
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 200 μL/min,进样量为 5 μL,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50~5 000 ng/mL(r=0.995 0);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 1 865.3~6 056.2 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。
关键词 超高效液相-串联质谱法;丙泊酚;淋巴水肿;血药浓度
Establishment of a method for detecting propofol concentration in plasma and its application in patients
with lymphedema
LI Jingfeng ,SHI Zhengyuan ,ZHANG Mengjie ,GUAN Lei ,JIANG Dechun(1. Dept. of Pharmacy, Beijing
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Shijitan Hospital Affiliated to Capital Medical Hospital, Beijing 100038, China;2. Dept. of Anesthesiology,
Beijing Shijitan Hospital Affiliated to Capital Medical Hospital, Beijing 100038, China)
ABSTRACT 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 200 μL/min. The sample size was 5 μL, 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 50-5 000 ng/mL (r=0.995 0). 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
1 865.3-6 056.2 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.
KEYWORDS UPLC-MS/MS; propofol; lymphedema; plasma concentration
Δ 基金项目 首都医科大学附属北京世纪坛医院淋巴外科开放
课题 丙泊酚是一种具有抗焦虑、调节免疫等作用的静脉
*第一作者 药师,博士。研究方向:临床治疗药物监测。电话: 麻醉药,其半衰期短、起效快,且麻醉后患者不适感较
010-63926405。E-mail:Lijf3692@bjsjth.cn
少,因此临床应用广泛 [1―2] 。但丙泊酚在临床应用中可
# 通信作者 主任药师,博士生导师,博士。研究方向:临床治疗药
[3]
物监测。电话:010-63926405。E-mail:jdc@bjsjth.cn 能会引起呼吸抑制、血流动力学不稳定等不良反应 ,尤
· 476 · China Pharmacy 2024 Vol. 35 No. 4 中国药房 2024年第35卷第4期