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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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                                                   1 #
          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
                                                     2
                                                                 2
                    1
                                    1
                                                                                1
          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
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