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

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 C-8 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 mu g/mL for 20 mu L 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).