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

作　　者：SHI Meiyun YIN Lei CAI Lanlan WANG Can LIU Xidong ZHAO Sen SUN Yantong FAWCETT J. Paul ZHAO Limei YANG Yan GU Jingkai 

机构地区：[1]College of Life Science, Jilin University, Changchun 130012, t~ R. China, [2]Clinical Pharmacology Center Research Institute of Translational Medicine, the First Hospital of Jilin University, Changchun 130061, 1~ R. China," [3]School of Pharmaceutical Sciences, dilin 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

出　　处：《Chemical Research in Chinese Universities》2014年第6期900-904,共5页高等学校化学研究（英文版）

基　　金：Supported by the National Natural Science Foundation of China（Nos.81430087, 81473142, 81102383） and the Prej ect 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 de- termination 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 ace- tonitrile/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 rain, respectively. The assay was linear over the concentration range of 0.1-100 gg/mL for 20 μL of human plasma only with intra- and inter-day preci- sions（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 l-h intravenous infusion of 1.0 g of cefotetan disodium for human volunteers（n=6）.A rapid and sensitive liquid chromatography-tandem mass spectrometry（LC-MS/MS） method for the de- termination 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 ace- tonitrile/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 rain, respectively. The assay was linear over the concentration range of 0.1-100 gg/mL for 20 μL of human plasma only with intra- and inter-day preci- sions（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 l-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 HUMANPLASMA 

分 类 号：TQ460.72[医药卫生—药物分析学] S859.796[化学工程—制药化工]