Characterization of Pharmaceutical Transformation Products by High-Field Asymmetric Waveform Ion Mobility and Infrared Ion Spectroscopy Coupled to Mass Spectrometry

Author(s)

Dantas, CesarA. G. ; Garcia, Pedro H. M. ; Correra, Thiago C.

• Document type: Journal article
• Source: JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY; v. 36, n. 6, p. 9-pg., 2025-05-12.

Abstract

The identification of drug degradation products is crucial for pharmaceutical development and quality control, as drug transformation products can significantly affect therapeutic efficacy and patient safety. Traditional analytical methods, such as high-performance liquid chromatography (HPLC) and tandem mass spectrometry (MS/MS), often require reference standards for accurate identification and may be unsuitable for resolving isomeric and isobaric degradation products. This study explores the use of high-field asymmetric waveform ion mobility spectrometry (FAIMS) and infrared multiple photon dissociation (IRMPD) spectroscopy coupled with mass spectrometry (MS) as an effective alternative for identifying drug degradation products without the need for previous chromatographic stages or the use of reference standards. Cyclophosphamide, a widely used DNA-alkylating agent in cancer and autoimmune therapies, is employed as a model system for this study. FAIMS enabled the separation of species based on their differential mobility, while IRMPD provided distinctive spectral data, allowing precise reference-standard-free structural elucidation. This integrated approach offers a robust solution for the identification of complex degradation products, advancing stability studies, formulation development, and quality control in pharmaceutical analysis. (AU)

• FAPESP's process: 21/06726-0 - Investigation of reactive intermediates in complex chemical and biochemical processes
• Grantee: Thiago Carita Correra
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 22/00498-8 - Multi-user equipment approved in grant 21/06726-0: ion mobility mass spectrometry system (IMS-MS)
• Grantee: Thiago Carita Correra
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 15/08539-1 - Multi-User Equipment approved in grant 2014/15962-5: ion trap mass spectrometer modified to perform infrared vibrational spectroscopy (IRMPD)
• Grantee: Thiago Carita Correra
• Support Opportunities: Multi-user Equipment Program
• FAPESP's process: 23/16303-4 - Development of a differential ion mobility device coupled to mass spectrometry for the evaluation of complex reactive systems
• Grantee: César Augusto Gonçalves Dantas
• Support Opportunities: Scholarships in Brazil - Post-Doctoral