Determination of total or free cefazolin and metronidazole in human plasma or interstitial fluid by HPLC-UV for pharmacokinetic studies in man

Cefazolin (CFZ) plus metronidazole (MTZ) is commonly used for perioperative antibiotic prophylaxis. An HPLC-UV method is described for the simultaneous determination of total or free cefazolin and metronidazole in human plasma or in microdialysate of subcutaneous tissue. Separation was performed isocratically using a reversed phase column and phosphate buffer/acetonitrile as mobile phase. The validation characteristics were similar for both drugs. Linearity has been shown down to 0.1 mg/L (R > 0.9990). Intra- and inter-assay precision (CV) and in-accuracy were < 5%. The method was applied to the determination of cefazolin and metronidazole in plasma and microdialysate of surgical patients following 30-min intravenous infusion of cefazolin/metronidazole 2.0/0.5 g.