salicylates and acetylsalicylsalicylic-acid

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.

Topics: Administration, Inhalation; Aerosols; Aspirin; Chemistry, Pharmaceutical; Chromatography; Reference Standards; Salicylates; Salicylic Acid; Solutions

Topics: Aspirin; Chromatography, High Pressure Liquid; Drug Stability; Hydrolysis; Salicylates; Solutions

Salicylsalicylic acid and acetylsalicylsalicylic acid were identified as decomposition products of aspirin when mixtures of the drug, with magnesium stearate, were stored in the solid state of 60 degrees and 75% relative humidity. The effect of increasing the concentration of magnesium stearate and the addition of other alkali stearates on the rate of decomposition of aspirin were studied. The validity of the theory that pH changes induced by the alkali stearates account for the catalytic effect of the lubricants on the decomposition was tested. The changes observed were modeled and the mechanism involved elucidated. The potential use of the melting points of aspirin mixtures in predicting the stability of the drug in such drug-excipient mixtures is demonstrated.

Topics: Aspirin; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Drug Stability; Excipients; Kinetics; Models, Chemical; Salicylates

A quantitative high-pressure liquid chromatographic method, using a reversed-phase column and an aqueous acetic acid-methanol solution as the mobile phase, was employed for the determination of O-acetyl-O-salicylsalicylic acid and O-salicylsalicylic acid in pharmaceutical aspirin preparations. The aspirin was dissolved, filtered, and injected into the chromatograph. The absorbance of the impurities was measured at 254 nm. Acetylsalicylic anhydridge was determined by a spectrophotometric method. The aspirin was dissolved in pH 11.3 buffer and extracted with benzene. An aliquot of the benzene was evaporated, and the residue was dissolved in alpha-benzamidocinnamate-pyridine reagent. The acetylsalicylic anhydride was measured using the difference between the absorbance at 362 and 372 nm. Possible interference of aspirin with the procedure is discussed. Thirty-four bulk aspirin and 172 tablet formulations were examined. Results for O-acetyl-O-salicylsalicylic acid, O-salicylsalicylic acid and acetylsalicylic anhydride are given.

Topics: Aspirin; Chromatography, High Pressure Liquid; Drug Contamination; Salicylates; Spectrophotometry