Continuous in-vivo monitoring of metronidazole in cerebrospinal fluid by a on-line flow-cell fiber-optic chemical sensor system

A new circulatory system for on-line and in-vivo monitoring of metronidazole in rabbit cerebrospinal fluid that makes use of a fiber-optic chemical sensor was presented. A metronidazole sensitive optrode was combined with a membrane onto which was immobilized pyrenebutyric acid as a fluoroprobe. Its concentration was determined via multiple quenching of the fluorescence of pyrenebutyric acid. The optrode shows a linear response from 2.0 to 100.0 μg ml−1 metronidazole in cerebrospinal fluid, the recoveries were 95.9~102.0%, the relative standard deviations were 1.0~3.9%, the detection limit was 0.47 μg ml−1 (SN = 3). The cerebrospinal fluid drug amount — time course in rabbit after oral administration conformed to a one-compartment open model with a first order absorption phase. The pharmacokinetic characteristics of metronidazole in cerebrospinal fluid were studied. The interferences were investigated and the selectivity of the method in rabbit cerebrospinal fluid was affirmed by a liquid Chromatographic method. The advantage of the instrument was discussed in terms of sensitivity, reversibility and stability. A new means of in-vivo therapeutic drug monitoring of cerebrospinal fluid from the brain of the conscious rabbit was also developed.