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高等学校化学研究 ›› 2014, Vol. 30 ›› Issue (6): 900-904.doi: 10.1007/s40242-014-4116-9

• Articles • 上一篇    下一篇

LC-MS/MS Method for the Quantitation of Cefotetan in Human Plasma and Its Application to Pharmacokinetic Study

SHI Meiyun1,2, YIN Lei1,2, CAI Lanlan1, WANG Can1, LIU Xidong1, ZHAO Sen1, SUN Yantong3, FAWCETT J. Paul4, ZHAO Limei5, YANG Yan1, GU Jingkai1,2   

  1. 1. College of Life Science, Jilin University, Changchun 130012, P. R. China;
    2. Clinical Pharmacology Center, Research Institute of Translational Medicine, the First Hospital of Jilin University, Changchun 130061, P. R. China;
    3. School of Pharmaceutical Sciences, Jilin University, Changchun 130021, P. R. China;
    4. School of Pharmacy, University of Otago, Dunedin 9054, New Zealand;
    5. The Second Clinical Hospital Affiliated to Chinese Medical University, Shenyang 110004, P. R. China
  • 收稿日期:2014-04-04 修回日期:2014-06-03 出版日期:2014-12-01 发布日期:2014-06-09
  • 通讯作者: GU Jingkai, YANG Yan E-mail:gujk@jlu.edu.cn;yyan@jlu.edu.cn
  • 基金资助:

    Supported by the National Natural Science Foundation of China(Nos.81430087, 81473142, 81102383) and the Preject of China Equipment and Education Resources System(CERS)(No.CERS-1-70).

LC-MS/MS Method for the Quantitation of Cefotetan in Human Plasma and Its Application to Pharmacokinetic Study

SHI Meiyun1,2, YIN Lei1,2, CAI Lanlan1, WANG Can1, LIU Xidong1, ZHAO Sen1, SUN Yantong3, FAWCETT J. Paul4, ZHAO Limei5, YANG Yan1, GU Jingkai1,2   

  1. 1. College of Life Science, Jilin University, Changchun 130012, P. R. China;
    2. Clinical Pharmacology Center, Research Institute of Translational Medicine, the First Hospital of Jilin University, Changchun 130061, P. R. China;
    3. School of Pharmaceutical Sciences, Jilin University, Changchun 130021, P. R. China;
    4. School of Pharmacy, University of Otago, Dunedin 9054, New Zealand;
    5. The Second Clinical Hospital Affiliated to Chinese Medical University, Shenyang 110004, P. R. China
  • Received:2014-04-04 Revised:2014-06-03 Online:2014-12-01 Published:2014-06-09
  • Contact: GU Jingkai, YANG Yan E-mail:gujk@jlu.edu.cn;yyan@jlu.edu.cn
  • Supported by:

    Supported by the National Natural Science Foundation of China(Nos.81430087, 81473142, 81102383) and the Preject of China Equipment and Education Resources System(CERS)(No.CERS-1-70).

摘要：

A rapid and sensitive liquid chromatography-tandem mass spectrometry(LC-MS/MS) method for the determination of cefotetan in human plasma was developed and validated. After the protein precipitation of sample with acetonitrile, the analyte and internal standard(IS), tramadol, were separated on a Zorbax XDB C8 column using acetonitrile/1%(volume fraction) formic acid(volume ratio 35:65, pH=2.5) as mobile phase at a flow rate of 1.0 mL/min with a 1:1 split. The detection was performed by electrospray ionization with positive ion mode, followed by multiple reaction monitoring of the transitions for cefotetan at m/z 576.3→460.2(quantifier) and m/z 576.3→432.2(qualifier) and for IS at m/z 264.1→58.1. Cefotetan and IS were eluted at 1.86 and 1.87 min, respectively. The assay was linear over the concentration range of 0.1―100 μg/mL for 20 μL of human plasma only with intra- and inter-day precisions(expressed as the relative standard deviation) of less than 6.62% and accuracies(as relative error) of ±1.31%. The method was applied to the pharmacokinetic study of a 1-h intravenous infusion of 1.0 g of cefotetan disodium for human volunteers(n=6).

关键词: Cefotetan, Liquid chromatography-tandem mass spectrometry(LC-MS/MS), Pharmacokinetics, Human plasma

Abstract:

A rapid and sensitive liquid chromatography-tandem mass spectrometry(LC-MS/MS) method for the determination of cefotetan in human plasma was developed and validated. After the protein precipitation of sample with acetonitrile, the analyte and internal standard(IS), tramadol, were separated on a Zorbax XDB C8 column using acetonitrile/1%(volume fraction) formic acid(volume ratio 35:65, pH=2.5) as mobile phase at a flow rate of 1.0 mL/min with a 1:1 split. The detection was performed by electrospray ionization with positive ion mode, followed by multiple reaction monitoring of the transitions for cefotetan at m/z 576.3→460.2(quantifier) and m/z 576.3→432.2(qualifier) and for IS at m/z 264.1→58.1. Cefotetan and IS were eluted at 1.86 and 1.87 min, respectively. The assay was linear over the concentration range of 0.1―100 μg/mL for 20 μL of human plasma only with intra- and inter-day precisions(expressed as the relative standard deviation) of less than 6.62% and accuracies(as relative error) of ±1.31%. The method was applied to the pharmacokinetic study of a 1-h intravenous infusion of 1.0 g of cefotetan disodium for human volunteers(n=6).

Key words: Cefotetan, Liquid chromatography-tandem mass spectrometry(LC-MS/MS), Pharmacokinetics, Human plasma