Quantification and Aerodynamic Particle Size Distribution of Revefenacin Aerosol With UHPLC-MS/MS

Abstract

Aerosol inhalation therapy offers significant benefits in treating chronic obstructive pulmonary disease, including rapid onset of action and reduced systemic side effects. Revefenacin, a long-acting bronchodilator, has demonstrated efficacy in improving lung function and alleviating chronic obstructive pulmonary disease symptoms through aerosol delivery. However, quantitative methods for determining the inhaled concentration of revefenacin aerosol remain limited. This study developed and validated a rapid, robust ultrahigh-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to quantify revefenacin aerosol concentration. The method, with an analysis time of 2 min, exhibited excellent specificity, precision, and a lower limit of quantification of 2 ng/mL. The aerosol extraction recovery averaged 98.5%. The method was successfully applied to assess aerosol concentration and aerodynamic particle size distribution under different sampling conditions. Results showed that after 15 min of nebulization, the average aerosol concentrations collected using syringe aspiration and impactor sampling methods were 0.98 and 0.95 mg/m³, respectively, demonstrating consistency between the techniques. Aerodynamic particle size distribution analysis revealed stable particle size distribution with atomization times of 5 and 15 min, yielding mass median aerodynamic diameters of 2.31 and 2.35 µm, fine particle fractions of 76.5% and 76.7%, and geometric standard deviations of 2.44 and 2.41, respectively. These findings indicate that the aerodynamic properties of revefenacin aerosol remain stable over prolonged nebulization. This study establishes a reliable analytical method for revefenacin aerosol quantification and provides valuable insights into its aerodynamic characteristics, supporting its further application in chronic obstructive pulmonary disease treatment.