Method development and validation for the GC-FID assay of ethanol in reservoir-type fentanyl transdermal patches

With ethanol acting as a skin permeation enhancer in the reservoir-type fentanyl transdermal delivery system, accurate assay of ethanol in the adapted cosolvent system is an important quality control component. This paper describes the development and validation of an isothermal gas chromatography-flame ionization detection (GC-FID) method for the assay of ethanol in reservoir-type fentanyl patches (Durogesic(superscript ®). Samples were extracted with water by ultrasonic vibration using acetone as the internal standard. Using a polar column (Supelco OVI-G43, 30 m×0.53 mm) for the gas chromatographic analysis, ethanol and excipients were well resolved. The method was fully validated according to the ICH Q2A and Q2B guidelines. The range of linearity for ethanol was demonstrated from approximately 0.1 to 0.9 mg/mL (r^2＞0.99). The accuracy (recovery tests at 60, 100, and 140% of the nominal analytical concentration of 0.5 mg/mL) was determined in the range of 98~101% with RSD≤0.75%. The precision (repeatability or intermediate precision) was calculated as RSD≤1.21%. The detection and quantitation limits were determined to be 1.99 and 6.03 μg/mL, respectively. Furthermore, the robustness and system suitability testing were also considered. In conclusion, a validated method for the assay of ethanol in reservoir-type fentanyl transdermal patches was successfully applied to quality control practices.