Forced degradation studies of corticosteroids with an alumina-steroid-ethanol model for predicting chemical stability and degradation products of pressurized metered-dose inhaler formulations.

An alumina (Al(2)O(3))-steroid-ethanol model is used for forced degradation testing of corticosteroids to predict chemical stability and degradation products in pressurized metered-dose inhaler (pMDI) solution formulations. The model involves an ethanolic solution of a test steroid with Al(2)O(3), stressed at elevated temperatures to mimic the chemical interaction of drug, excipient, and packaging (an aluminum aerosol canister). The reactivity order of eight synthetic corticosteroids toward Al(2)O(3)-induced reactions is ranked with the stress model. The corticosteroids containing a C21-OH group possess the highest reactivity, suggesting that aluminum canisters with an inert interior coating are needed to stabilize their solution pMDIs. The Al(2)O(3)-induced degradation products and degradation pathways of a steroid containing C21-OH and triamcinolone acetonide are presented, and the role of Al(2)O(3) in the degradation pathways is briefly discussed. A potential degradation profile of beclomethasone dipropionate (BDP) established with an Al(2)O(3)-BDP-ethanol stress model is the same as the actual degradation profile of the BDP pMDI product, indicating that the model indeed predicts the degradation products.

Determination of perfluorinated compounds in fish fillet homogenates: method validation and application to fillet homogenates from the Mississippi River.

We report herein a simple protein precipitation extraction-liquid chromatography tandem mass spectrometry (LC/MS/MS) method, validation, and application for the analysis of perfluorinated carboxylic acids (C7-C12), perfluorinated sulfonic acids (C4, C6, and C8), and perfluorooctane sulfonamide (FOSA) in fish fillet tissue. The method combines a rapid homogenization and protein precipitation tissue extraction procedure using stable-isotope internal standard (IS) calibration. Method validation in bluegill (Lepomis macrochirus) fillet tissue evaluated the following: (1) method accuracy and precision in both extracted matrix-matched calibration and solvent (unextracted) calibration, (2) quantitation of mixed branched and linear isomers of perfluorooctanoate (PFOA) and perfluorooctanesulfonate (PFOS) with linear isomer calibration, (3) quantitation of low level (ppb) perfluorinated compounds (PFCs) in the presence of high level (ppm) PFOS, and (4) specificity from matrix interferences. Both calibration techniques produced method accuracy of at least 100±13% with a precision (%RSD) ≤18% for all target analytes. Method accuracy and precision results for fillet samples from nine different fish species taken from the Mississippi River in 2008 and 2009 are also presented.