The aim of this study was to develop and validate a high-performance liquid
chromatography method for the determination of tricyclic antidepressants i
n skin permeation studies. The chromatographic system involved the use of a
Shim-pack (C-18) column with pH 3.0 sodium phosphate buffer-acetonitrile a
s the mobile phase; detection was set at 238 and 250 nm for amitriptyline H
Cl and imipramine HCl, respectively. Calibration curves of amitriptyline HC
l and imipramine HCl were obtained in three different media namely, methano
l, pH 7.4 phosphate buffer and physiological saline. Skin permeation studie
s were peformed using Sprague-Dawley rat skin and drug samples were analyse
d by the HPLC method. this technique was compared with radiochemical analys
is using H-3 imipramine. The HPLC method proposed was successfully applicab
le to the continuous monitoring of tricyclic antidepressants in skin permea
tion studies, and the results were comparable to the radiochemical method i
n the case of imipramine HCl.