Simultaneous determination of cefazolin in rat blood and brain by microdialysis and microbore liquid chromatography.
A sensitive microbore liquid chromatographic method combined with the minimally invasive technique of microdialysis was devised for simultaneously and continuously monitoring the levels of unbound blood and brain cefazolin in rats. Microdialysis probes were inserted into the jugular vein and brain striatum for blood and brain sampling, respectively. Chromatographic conditions consisted of a mobile phase of methanol-acetonitrile-100 mM monosodium phosphoric acid (20:10:70, v/v, pH 4.5) pumped through a microbore reversed-phase column at a flow rate of 0.05 mL/min. The ultraviolet detection wavelength was set at 270 nm. An on-line design allowed direct and continuous analysis of protein-free samples in the dialysate. Microdialysis probes, being home-made, were screened for acceptable in vivo recovery. Chromatographic resolution and detection were validated for response linearity as well as intra-day and inter-day variabilities. This method was then applied to pharmacokinetic profiling of protein unbound cefazolin in both the blood and brain following intravenous administration (10 mg/kg, i.v., n = 6). Rapid appearance of cefazolin in the rat brain striatal dialysate following drug injection suggested good blood-brain barrier penetration. According to a non-compartmental pharmacokinetics model, the area under the concentration (AUC) vs time ratio of cefazolin in rat brain and blood was 6%.
Tsai
T H
TH
Department of Pharmacology, National Research Institute of Chinese Medicine, Taipei 112, Taiwan. thtsai@cma23.nricm.edu.tw
Chen
Y F
YF
D000818:Animals; D001921:Brain / Q000378:metabolism*; D002437:Cefazolin / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D002511:Cephalosporins / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D007202:Indicators and Reagents; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
D002511:Cephalosporins; D007202:Indicators and Reagents; D002437:Cefazolin