Simple liquid chromatographic method for the analysis of the blood brain barrier permeability characteristics of ceftriaxone in an experimental rabbit meningitis model

A simple LC method was developed and validated for the analysis of ceftriax one in aqueous and biological samples. Chromatographic separation was achie ved on a reversed-phase C-18 microbore column (Hypersil 5 mu m, 200x2.1 mm) with UV detection at 270 nm. This isocratic system was operated at ambient temperature and required less than 10 min of chromatographic time. The flo w-rate was maintained at 0.5 mi min(-1). Cetyltrimethylammonium bromide (0. 01 M) was utilized as the ion-pairing agent. For the analysis of the drug i n the aqueous system, the mobile phase consisted of methanol-acetonitrile-p hosphate buffer, pH 7.4 (20:20:60, v/v/v). The plasma and CSF systems used the same mobile phase constituents in a slightly different ratio (30:40:30, v/v/v). Lidocaine was used as an internal standard and the peak height rat ios of the drug to that of the internal standard were linear over the conce ntration range of 0.0 to 16 mu g ml(-1) only in the case of aqueous systems . Within-day and day-to-day relative standard deviations ranged from 0.3 to 2.2% and 1.1 to 5.9%, respectively. This method was used to: (1) quantify ceftriaxone in an aqueous system, in rabbit plasma using a simple protein p recipitation procedure, and in the CSF; (2) evaluate the permeability chara cteristics of ceftriaxone across the blood-brain barrier through quantifica tion of ceftriaxone in the CSF using a microdialysis sampling technique; an d (3) analyze the effects of dexamethasone (a synthetic fluorinated cortico steroid used for the relief of cerebral edema) on the permeability of ceftr iaxone across the blood brain barrier through quantification of ceftriaxone in the dexamethasone-treated animals with meningitis. (C) 1999 Elsevier Sc ience B.V. All rights reserved.