Gas chromatography has been used for analysis of aerosol propellants and active ingredients. The propellant analysis generally involved introduction of a previously vaporized sample into the gas chromatograph. Such methods become impractical when dealing with small aerosol packages such as those used for inhalation therapy. The purpose of this work was to develop methods for the accurate sampling and analysis of the propellants and cosolvents of such packages. These methods may also be extended to other volatile components of aerosol packages. Two sampling techniques were developed. These include the use of gas-tight sampling devices to either prepare solutions of the aerosol contents or to load a smallvolume, high-pressure, liquid syringe. The volatile components were separated on a porous polystyrene bead column and the composition was calculated from peak areas.
RESSURIZED AEROSOLS used for inhalation P therapy generally are packaged in small containers fitted with metered valves. Accurate sampling of such packages and analysis of the volatile constituents, contained therein, are difficult, since the composition of a small volume of such mixtures in the liquid phase can change considerably by fractionating as it volatilizes.
The aerosols may contain a wide boiling range of solvents, from propellant 12, b.p. -29.8", to some of the glycols with boiling points in excess of 200'. To further complicate matters, the metered valve does not provide a convenient access to sample for such analyses.
Prior to the development of gas chromatography, aerosol propellants were analyzed by several methods such as mass spectrometry, infrared spectrophotometry, liquid density measurements, and vapor pressure determinations (I). Gas chromatography has been utilized for the past decade for the analysis of halogenated hydrocarbons such as used in aerosols (I, 2, 4, 7)
and for the analysis of other ingredients in pharmaceutical aerosols (3, 6).
Percival (1) and Thonet (7) used variations of gas sampling systems to obtain samples of aerosol propellants in the vapor state prior to introduction into the gas chromatograph. The components were subsequently separated on di-n-octyl phthalate or alumina columns in the former work and on a di-n-butyl maleate column in the latter. The use of metered valves makes these methods impractical. There is also the possibility of condensation of the higher boiling