The quantitative determination of aspirin and its degradation products in a model solution aerosol

Formulation of pressurized aerosol solutions in propellants for inhalation requires the use of high quantities of surfactants to solubilize the drug. Due to the lipophilic nature of these surfactants, analytical difficulties are created for those wishing to quantify the drug and its degradation products. In order to quantify drug and degradation products by LC it is necessary to separate surfactant and analytes prior to chromatography. To illustrate a typical situation, a method was developed for the analysis of acetylsalicyclic acid (approximately 2.5 x 10(-3) M) and its major degradation products (salicylic acid, acetylsalicylsalicylic acid and salicylsalicylic acid) solubilized in trichloromonofluoromethane (CFC-11) containing 10(-2) M sorbitan trioleate (Span 85). Surfactant extraction problems were reviewed experimentally. The presentation of all analytes and the surfactant, dissolved in hexane, to silica solid phase extraction columns, followed by elution in a polar solvent, was found to be an efficient way of separating this lipophilic surfactant from the analytes. The final assay employed propellant evaporation, reconstitution of the non-volatiles in hexane, normal phase solid phase extraction (recoveries of 100 +/- 10% were observed for all analytes), elution and dilution with mobile phase, and reversed-phase liquid chromatography (Econosphere C8 5 microns, 4.6 x 250 mm). The assay utilized a mobile phase of water, methanol, tetrahydrofuran and 1 M phosphoric acid with ultraviolet detection at 275 nm. Using external standards, linear calibration curves of peak height versus concentration were obtained for all analytes in the expected concentration ranges (r > 0.991). As it is described, the assay had a relative standard deviation of < or = 3.7% for all analytes.