Sawaki Kohei, Okubo Migiwa, Shimomiya Takashi, Tukagoshi Eri, Sakai Takayuki, Yamazaki Takaki, Kenmochi Masahiro, Miyao Mariko, Kaneko Yuzuru, Ichinohe Tatsuya, Kawaguchi Mitsuru
Department of Pharmacology, Tokyo Dental College, Chiba, Japan.
Biomed Res. 2009 Dec;30(6):319-24. doi: 10.2220/biomedres.30.319.
We studied the viability of high-performance liquid chromatography and mass spectrometry (LC/MS) as a selective and sensitive analytical method for measuring blood concentrations of the local anesthetic ropivacaine. Ropivacaine was effectively separated using a reverse-phase column and monitored at 275 m/z ion. The LC/MS method allowed measurement of concentrations of ropivacaine of lower than 75 ng/mL. The standard curve was linear and in the range of <1.5 microg/mL. Recovery of ropivacaine in plasma samples was over 90% after precipitation of plasma protein with trichloroacetic acid. The method was tested on the pharmacokinetics of plasma ropivacaine after single intravenous or subcutaneous administration in rabbits. The pharmacokinetic parameters showed a one-compartment model and a mean elimination half-life of 0.54+/-0.05 h and 2.83+/-0.51 h after administration at doses of 0.4 mg/kg, i.v. and 5 mg/kg, s.c., respectively. These values were in approximate agreement with previously obtained results in dogs. The results of the present study demonstrated that the LC/MS method was highly selective and sensitive for the measurement of ropivacaine, indicating that it offers a useful tool for monitoring the therapeutic effects and determining the pharmacokinetic parameters of this drug in blood.
我们研究了高效液相色谱-质谱联用技术（LC/MS）作为一种选择性和灵敏性的分析方法来测定局麻药罗哌卡因血药浓度的可行性。使用反相柱可有效分离罗哌卡因，并在275 m/z离子处进行监测。LC/MS方法能够测定低于75 ng/mL的罗哌卡因浓度。标准曲线呈线性，范围为<1.5 μg/mL。用三氯乙酸沉淀血浆蛋白后，血浆样本中罗哌卡因的回收率超过90%。该方法在兔单次静脉注射或皮下注射后血浆罗哌卡因的药代动力学研究中得到验证。药代动力学参数显示为一室模型，静脉注射剂量为0.4 mg/kg、皮下注射剂量为5 mg/kg后，平均消除半衰期分别为0.54±0.05小时和2.83±0.51小时。这些数值与先前在犬身上获得的结果大致相符。本研究结果表明，LC/MS方法对罗哌卡因的测定具有高度选择性和灵敏性，表明它为监测该药物的治疗效果和确定其在血液中的药代动力学参数提供了一种有用的工具。
