Simultaneous Determination of Etretinate, Acitretin and 13-cis-Acitretin in Plasma by Gradient-HPLC Using Automated Column Switching

Abstract

Etretinate (Tigason®), an aromatic retinoid ethyl ester, is an oral dermatological drug which is effective in the treatment of psoriasis and other keratinizing disorders [1]. It is hydrolyzed to the corresponding acid in vivo [2]. This metabolite, acitretin, (Neotigason®), has a much shorter elimination half-life and shows the same activity in clinical studies; it will succeed etretinate as a drug in the near future. It furnishes 13-cis-acitretin by isomerization in vivo [2]. Therapeutic drug monitoring is important for this class of compounds because of teratogenicity problems and other side-effects; however, sample handling is difficult in view of the light-sensitivity and the very high protein binding (>99.9%) of the retinoids. Accordingly, an automated method involving gradient elution, column switching and UV detection at 360 nm similar to that described for isotretinoin and its metabolites [3], has been developed for the determination of etretinate, acitretin and 13-cis-acitretirin.