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.

Serum concentrations of perfluorooctanesulfonate and other fluorochemicals in an elderly population from Seattle, Washington.

Perfluorooctanesulfonyl fluoride (POSF, C8F17SO2F) related-materials have been used as surfactants, paper and packaging treatments, and surface (e.g., carpet, textile, upholstery) protectants. A metabolite, perfluorooctanesulfonate (PFOS, C8F17SO3-), has been identified in the serum and liver of non-occupationally exposed humans and wildlife. Because of its persistence, an important question was whether elderly humans might have higher PFOS concentrations. From a prospective study designed to examine cognitive function in the Seattle (WA) metropolitan area, blood samples were collected from 238 dementia-free subjects (ages 65-96). High-pressure liquid chromatography-electrospray tandem mass spectrometry determined seven fluorochemicals: PFOS; N-ethyl perfluorooctanesulfonamidoacetate; N-methyl perfluorooctanesulfonamidoacetate; perfluorooctanesulfonamidoacetate; perfluorooctanesulfonamide; perfluorooctanoate; and perfluorohexanesulfonate. Serum PFOS concentrations ranged from less than the lower limit of quantitation (3.4 ppb) to 175.0 ppb (geometric mean 31.0 ppb; 95% CI 28.8-33.4). An estimate of the 95% tolerance limit was 84.1 ppb (upper 95% confidence limit 104.0 ppb). Serum PFOS concentrations were slightly lower among the most elderly. There were no significant differences by sex or years residence in Seattle. The distributions of the other fluorochemicals were approximately an order of magnitude lower. Similar to other reported findings of younger adults, the geometric mean serum PFOS concentration in non-occupational adult populations likely approximates 30-40 ppb with 95% of the population's serum PFOS concentrations below 100 ppb.

Perfluorooctanesulfonate and other fluorochemicals in the serum of American Red Cross adult blood donors.

Perfluorooctanesulfonyl fluoride-based products have included surfactants, paper and packaging treatments, and surface protectants (e.g., for carpet, upholstery, textile). Depending on the specific functional derivatization or degree of polymerization, such products may degrade or metabolize, to an undetermined degree, to perfluorooctanesulfonate (PFOS), a stable and persistent end product that has the potential to bioaccumulate. In this investigation, a total of 645 adult donor serum samples from six American Red Cross blood collection centers were analyzed for PFOS and six other fluorochemicals using HPLC-electrospray tandem mass spectrometry. PFOS concentrations ranged from the lower limit of quantitation of 4.1 ppb to 1656.0 ppb with a geometric mean of 34.9 ppb [95% confidence interval (CI), 33.3-36.5]. The geometric mean was higher among males (37.8 ppb; 95% CI, 35.5-40.3) than among females (31.3 ppb; 95% CI, 30.0-34.3). No substantial difference was observed with age. The estimate of the 95% tolerance limit of PFOS was 88.5 ppb (upper limit of 95% CI, 100.0 ppb). The measures of central tendency for the other fluorochemicals (N-ethyl perfluorooctanesulfonamidoacetate, N-methyl perfluorooctanesulfonamidoacetate, perfluorooctanesulfonamidoacetate, perfluorooctanesulfonamide, perfluorooctanoate, and perfluorohexanesulfonate) were approximately an order of magnitude lower than PFOS. Because serum PFOS concentrations correlate with cumulative human exposure, this information can be useful for risk characterization.