A rapid and simple capillary zone electrophoresis (CZE) method for the dete
rmination of terbinafine and eight of its main metabolites after incubation
with rat hepatic S9 fraction was developed. The effect of the concentratio
n and type of the running electrolyte as well as of the addition of an orga
nic solvent were studied with emphasis on selectivity and sensitivity. All
nine components obtained (unmetabolized terbinafine and up to eight of its
metabolites) are baseline resolved in less than 4 minutes using a 0.05 M ph
osphate buffer (pH 2.2) without additives, after a solid-phase clean-up pro
cedure of these in-vitro samples. In addition, under the conditions describ
ed, no endogenous components of the sample interfere at the detection wavel
ength chosen. After optimization of the separation conditions, some analyti
cal characteristics of the developed CZE method were investigated. A limit
of detection of only 0.08 mug/mL was obtained for terbinafine using a stand
ard solution. Finally, the use of on-line CZE/ diode array detection enable
d to identify tentatively the presence of unmetabolized parent terbinafine
and its metabolites in the mixture of nine components separated.