Rapid and simple method for determination of cephradine in human plasma using liquid chromatography–tandem mass spectrometry (LC–MS/MS): Application to the bioequivalence study

A rapid and simple procedure was developed for the determination of cephradine in human plasma using liquid chromatography coupled with electrospray ionization-tandem mass spectrometry (LC–ESI-MS/MS). After trichloroacetic acid (TCA) precipitation of proteins from plasma samples, cephradine and cefaclor (the internal standard; IS) were eluted on a CN column. The isocratic mobile phase used consisted of acetonitrile–water–formic acid (25:75:0.1, v/v/v). Cephradine and the IS were both detected in multiple reaction monitoring (MRM) mode at the transitions: m/z 350.0 → 90.8 for cephradine and m/z 368.1 → 106.0 for the IS, respectively. The calibration curve was linear over the concentration range from 0.05 to 50 μg/ml, and correlation coefficients were greater than 0.996. The coefficient of variation of assay precision was less than 9.36%, and its accuracy ranged from 87.92% to 111.16%. The chromatographic run time for each plasma sample was less than 3 min. The developed method was successfully applied to a bioequivalence study of cephradine in healthy male volunteers.