Simultaneous blood and brain sampling of cephalexin in the rat by microdialysis and microbore liquid chromatography: application to pharmacokinetics studies.
To circumvent the need for laborious sample clean-up and multiple blood sampling, a system was developed consisting of on-line microdialysis coupled to microbore liquid chromatography and ultraviolet detection. The system was designed for the simultaneous and continuous monitoring of unbound blood and brain cephalexin in the rat following single bolus intravenous administrations (10 mg/kg, n = 6). Microdialysis probes were inserted into the jugular vein and brain striatum, respectively, for blood and brain sampling. Chromatographic conditions consisted of a mobile phase of methanol-100 mM monosodium phosphoric acid (20:80, v/v, pH 5.0) pumped through a microbore reversed-phase column at a flow-rate of 0.05 ml/min. Detection wavelength was set at 260 nm. The method was validated for response linearity as well as intra- and inter-day variabilities. Rapid appearance of cephalexin in the striatal dialysate suggested good blood-brain barrier penetration. This study provided pharmacokinetics information for cephalexin as well as demonstrated the applicability of this continuous sampling method for pharmacokinetics studies.
Tsai
T H
TH
Department of Pharmacology, National Research Institute of Chinese Medicine, Taipei, Taiwan. thtsai@cma23.nricm.edu.tw
Hung
L C
LC
Chang
Y L
YL
Shum
A Y
AY
Chen
C F
CF
D000818:Animals; D019540:Area Under Curve; D001923:Brain Chemistry; D002506:Cephalexin / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics*; D002511:Cephalosporins / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D008297:Male; D017551:Microdialysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
D002511:Cephalosporins; D007202:Indicators and Reagents; D002506:Cephalexin