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

• Published in: Chemical research in Chinese universities Vol. 30; no. 6; pp. 900 - 904
• Main Authors: Shi, Meiyun, Yin, Lei, Cai, Lanlan, Wang, Can, Liu, Xidong, Zhao, Sen, Sun, Yantong, Fawcett, Paul J., Zhao, Limei, Yang, Yan, Gu, Jingkai
• Format: Journal Article
• Language: English
• Published: Heidelberg Jilin University and The Editorial Department of Chemical Research in Chinese Universities 01.12.2014; Clinical Pharmacology Center, Research Institute of Translational Medicine, the First Hospital of Jilin University,Changchun 130061, P.R.China%College of Life Science, Jilin University, Changchun 130012, P.R.China%School of Pharmaceutical Sciences, Jilin University, Changchun 130021, P.R.China; College of Life Science, Jilin University, Changchun 130012, P.R.China
• Subjects: Analytical Chemistry; Chemistry; Chemistry and Materials Science; Chemistry/Food Science; Inorganic Chemistry; LC-MS; Organic Chemistry; Physical Chemistry; S方法; 人血浆; 头孢; 应用; 相对标准偏差; 药代动力学; 蛋白质沉淀; Cefotetan; Human plasma; Pharmacokinetics; Liquid chromatography-tandem mass spectrometry(LC-MS/MS)
• ISSN: 1005-9040; 2210-3171
• DOI: 10.1007/s40242-014-4116-9

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）.