ABSTRACT
Organic compounds extracted into metered dose inhalers (MDIs) from the rubber components of the metering valve are of increasing interest in the development of these formulations. Polycyclic aromatic hydrocarbons (PAHs) are a class of extractable organic compounds whose source is the carbon black commonly used as a reinforcing agent in rubber. The analytical method for PAHs described in this report employs "cold filtration" to remove the suspended drug substance and excipients, and gas chromatography/mass spectrometry (GC/MS) for separation and detection of individual PAHs. After filtration, stable isotope labelled analogues of target PAHs are spiked into the drug product to act as internal standards, correcting for recovery (termed "isotope dilution GC/MS"). Validation of the method was accomplished with respect to linearity, precision, limit of detection/quantitation, selectivity and ruggedness. Application to a variety of MDI drug product formulations revealed that certain PAHs are present at the ng/inhaler level.
Subject(s)
Polycyclic Compounds/analysis , Gas Chromatography-Mass Spectrometry , Indicators and Reagents , Nebulizers and Vaporizers , Radioisotope Dilution Technique , Reference Standards , SolutionsABSTRACT
An indirect photometric ion chromatography method is developed for the quantitation of oxalate in typical pharmaceutical matrices. The column/mobile phase conditions used represent a trade off between resolving power and sensitivity and results in an assay with a total analysis time of less than 9 minutes. Method response is linear between concentrations of 10 to 80 ppm oxalate. The limit of quantitation is roughly 5 ppm. Precision in the range of 30 to 80 ppm is better than 1.0% RSD of replicate injections, and the accuracy in a variety of matrices is 100 +/- 2%. The method is quite rugged and meets rigorous suitability requirements even after 500 injections. Although the assay can be used to quantitate citrate as well, the retention time is relatively long (20 minutes) and sensitivity is limited due to the broadness of the peak.
