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

Autor(es)

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

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY; v. 36, n. 6, p. 9-pg., 2025-05-12.

Resumo

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)

• Processo FAPESP: 21/06726-0 - Investigação de intermediários reativos em processos químicos e bioquímicos complexos
• Beneficiário: Thiago Carita Correra
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2
• Processo FAPESP: 22/00498-8 - EMU concedido no processo 21/06726-0: sistema de mobilidade iônica acoplada à espectrometria de massas (IMS-MS)
• Beneficiário: Thiago Carita Correra
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 15/08539-1 - EMU concedido no processo 2014/15962-5: espectrômetro de massas tipo íon TRAP modificado para realização de espectroscopia vibracional no infravermelho (IRMPD)
• Beneficiário: Thiago Carita Correra
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários
• Processo FAPESP: 23/16303-4 - Desenvolvimento de um sistema de mobilidade iônica acoplada a espectrometria de massas para avaliação de sistemas reativos complexos
• Beneficiário: César Augusto Gonçalves Dantas
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado