Real-time metered dose inhalers (MDIs) characterization by secondary electrospray ionization (SESI)-mass spectrometry: a proof-of-principle study.

This study explores the application of secondary electrospray ionization mass spectrometry (SESI-MS) for the real-time characterization of pharmaceutical aerosols from metered-dose inhalers (MDIs). The analysis includes one of the most widely used inhalers worldwide, Ventolin®, a simple formulation containing salbutamol and norflurane for which salbutamol was reliably detected, while norflurane remained undetectable due to its low proton affinity; and Ventoduo®, a multicomponent formulation also including beclomethasone dipropionate, ethanol, and oleic acid for which all major components were successfully detected. The coupling of SESI with high-resolution MS enabled unambiguous identification of all analytes, with excellent mass accuracy, confirming the identity of both active ingredients through characteristic fragmentation patterns. These results demonstrate that SESI-MS, particularly when coupled with high-resolution instrumentation (SESI-HRMS), is a powerful and reliable tool for the comprehensive and real-time analysis of pharmaceutical aerosols, including those with multiple active ingredients and co-solvents.