Abstract
To analyze unbound cefamandole in rat blood, a method combing microdialysis with microbore liquid chromatography has been developed. A microdialysis probe was inserted into the jugular vein/right atrium of male Sprague–Dawley rats to examine the unbound cefamandole level in the rat blood following cefamandole administration (50 mg/kg, i.v.). The dialysates were directly submitted to a liquid chromatographic system. Samples were eluted with a mobile phase containing acetonitrile–methanol–100 mM monosodium phosphate (pH 5.0; 15:20:65, v/v). The UV wavelength was set at 270 nm for monitoring the analyte. Using the retrograde method, at infusion concentrations of 1 µg/mL of cefamandole, the in vivo microdialysis recoveries were 55.44% for the rat blood (n = 6). Intra‐ and inter‐assay accuracy and precision of the analyses were ≤10% in the range of 0.1–10 µg/mL. Pharmacokinetic parameters were calculated from the recovery‐corrected dialysate concentrations of cefamandole vs time data. The elimination half‐life (t~1/2,β~) was 21.6 ± 1.6 min. The results suggest that the pharmacokinetics of unbound cefamandole in blood following cefamandole administration (50 mg/kg, i.v., n = 5) fit best to the two‐compartmental model. Copyright © 2001 John Wiley & Sons, Ltd.
Abbreviations used:
RSD
relative standard deviation