Validation and Application of an LC–MS-MS Method for the Determination of Ceftizoxime in Human Serum and Urine

Ceftizoxime sodium is a third-generation cephalosporin available for parenteral administration, which is mainly excreted through urine. A rapid and sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UPLC–MS-MS) method was developed and validated for the determination of ceftizoxime in human serum and urine. The samples were purified by protein precipitation and separated on an XTerra Phenyl column (4.6×50 mm, 5 µm). Electrospray ionization in the positive ion mode and multiple reaction monitoring were used to monitor the ion transitions at m/z 383.9/227.0. The results revealed that the method had excellent selectivity. The linear range covered from 2.50 to 10,000 ng/mL in serum and from 0.500 to 50.0 µg/mL in urine, respectively. Intra-batch and inter-batch precisions (in terms of relative standard deviation) were all <15% and the accuracies (in terms of relative error) were within the range of ±15%. The lower limit of quantification, stability and extraction recovery were also validated and satisfied the criteria of validation. Finally, the method was successfully applied to a pharmacokinetic study of Chinese elderly healthy subjects after intravenous administration. The Cmax values in serum were 34,721.3 ± 5,697.3 ng/mL. Serum concentrations declined with t1/2 of 2.57 ± 0.22 h.