Determination of cefdinir levels in rat plasma and urine by high-performance liquid chromatography-tandem mass spectrometry: application to pharmacokinetics after oral and intravenous administration of cefdinir.

A selective and sensitive liquid chromatography tandem mass spectrometry method (LC-MS/MS) was developed and validated for the determination of cefdinir in rat plasma and urine. Following a simple protein precipitation using methanol, chromatographic separation was achieved with a run time of 10 min using a Synergi 4 µ polar-RP 80A column (150 × 2.0 mm, 4 µm) with a mobile phase consisting of 0.1% formic acid in water and methanol (65:35, v/v) at a flow rate of 0.2 mL/min. The protonated precursor and product ion transitions for cefdinir (m/z 396.1 → 227.2) and cefadroxil, an internal standard (m/z 364.2 → 208.0) were monitored in the multiple reaction monitoring in positive ion mode. The calibration curves for plasma and urine were linear over the concentration range 10-10,000 ng/mL. The lower limit of quantification was 10 ng/mL. All accuracy values were between 95.1 and 113.0% and the intra- and inter-day precisions were <13.0% relative standard deviation. The stability under various conditions in rat plasma and urine was also found to be acceptable at three concentrations. The developed method was applied successfully to the pharmacokinetic study of cefdinir after oral and intravenous administration.