A novel in-vitro technique for studying percutaneous permeation with a membrane-coated fiber and gas chromatography/mass spectrometry: part L performances of the technique and determination of the permeation rates and partition coefficients of chemic

摘要

PURPOSE: To develop a novel in-vitro technique for rapid assessment of percutaneous absorption of chemical mixtures. METHODS: A silastic membrane was coated on to a fiber to be used as a permeation membrane. The membrane-coated fiber was immersed in the donor phase to partition the compounds into the membrane. At a given partition time, the membrane-coated fiber was transferred into a GC injector to evaporate the partitioned compounds for quantitative and qualitative analyses. RESULTS: This technique was developed and demonstrated to study the percutaneous permeation of a complex mixture consisting of 30 compounds. Each compound permeated into the membrane was identified and quantified with GC/MS. The standard deviation was less than 10% in 12 repeated permeation experiments. The partition coefficients and permeation rates in static and stirred donor solution were obtained for each compound. The partition coefficients measured by this technique were well correlated (R2 = 0.93) with the reported octanol/water partition coefficients. CONCLUSIONS: This technique can be used to study the percutaneous permeation of chemical mixtures. No expensive radiolabeled chemicals are required. Each compound permeated into the membrane can be identified and quantified. The initial permeation rate and equilibrium time can be obtained for each compound, which could serve as characteristic parameters regarding the skin permeability of the compound.