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

利用高场非对称波形离子迁移谱和红外离子光谱联用质谱技术对药物转化产物进行表征

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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.

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