Determination of Acitretin in the Skin, in the Suction Blister, and in Plasma of Human Volunteers after Multiple Oral Dosing

Abstract

Several HPLC methods for quantification of acitretin and its 13‐cisisomer in biological fluids have been described. Only limited data are available on determination of this drug in skin samples. Our objective was to improve the sensitivity and selectivity of existing methods to measure drug in small skin samples from humans treated with acitretin. With a new optimized mobile phase [methanol: acetonitrile (7:3, v/v), purified water with 1.5% (v/v) acetic acid, mixed in a 85:15 ratio (v/v)] and a new internal standard (arotinoid ethyl sulfone), a limit of quantification of 1 ng/g tissue was reached. Nine male volunteers were given an oral daily dose of 50 mg acitretin for up to 28 days. Blood and skin samples (punch and shave biopsies, suction blister skin, and fluid) were taken at various time points during and after treatment. Drug concentration and metabolism in plasma and skin samples appeared to be linked in that thetrans‐isomer concentration was always higher than thecis‐isomer concentration during dosing and 3 h after the last dose. However, 7 and 14 days after the last dose in plasma and in all tissue samples (except the shave biopsy), the all‐trans‐acitretin concentration rapidly decreased and approached the detection limit. In the shave biopsy, the all‐trans‐acitretin concentration remained higher than the 13‐cis‐acitretin concentration. Furthermore, the elimination of two isomers from the shave biopsy was delayed. Our HPLC method has provided a suitable tool for pharmacokinetic and drug monitoring studies of all‐trans‐acitretin and 13‐cis‐acitretin that can be performed by any laboratory with a darkroom and abasic isocraticHPLC system.