Single Particle Characterization of Albuterol Metered Dose Inhaler Aerosol in Near Real-Time

Abstract

Metered dose inhalers produce a fine spray of aerosol particles that are used as an inhalation drug delivery system for a variety of therapeutic purposes. Common analytical methods employed for characterizing the aerosol dosage are typically off-line analyses for both chemical information and particle size distributions, and focus on the bulk aerosol rather than on single particles. Aerosol time-of-flight mass spectrometry offers the capability to analyze the aerosol dose in near real-time, providing both size and chemical information for single particles. Though aerosol time-of-flight mass spectrometry has been used primarily to characterize environmental samples, this is the first demonstration of its bioanalytical capabilities. This paper discusses the characterization of an albuterol metered dose inhaler using both high and low laser power for the desorption/ionization process in order to control the amount of fragmentation observed in the mass spectral analysis. Using high laser power, significant fragmentation occurs with no major ion peaks above mass-to-charge 100 Da. In contrast, lower laser power allows for the observation of protonated and deprotonated parent ion in positive and negative ion analysis respectively. Also, high mass daughter ions are apparent in both positive and negative ion analysis.