A Comprehensive LC-MS/MS Method for Detecting Genotoxic Nitrosamine Impurities in Favipiravir API
1,2, 1, 1, 3
- 1Department of Pharmacy, Jiangsu Medical College, Yancheng, Jiangsu, People’s Republic of CHINA.
- 2Post Graduate Centre, Management and Science University, University Drive, Off Persiaran Olahraga, Selangor, MALAYSIA.
- 3Department of Diagnostic and Allied Health Science, Faculty of Health and Life Sciences, Management and Science University, Shah Alam, MALAYSIA.
- 4Jinling Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, People’s Republic of CHINA.
CORRESPONDENCE
Dr. Guntupalli Chakravarthi
Department of Pharmaceutical Analysis, KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, Guntur, Andhra Pradesh, INDIA.
Received: 24-06-2024; Revised: 26-07-2024; Accepted: 20-12-2024.
Volume 59, Issue 1s (Supplement) · pp. s256-s263 · 2025 · DOI: 10.5530/ijper.20250167
ABSTRACT
Background: Favipiravir, a purine nucleic acid analogue (T-705), was used to treat SARS-CoV-2 patients. Existing methods often target specific nitrosamines in various matrices but not necessarily Favipiravir. These findings highlight the lack of a comprehensive method for detecting all seven potential nitrosamine impurities in Favipiravir API.Materials and Methods: The current approach discusses the trace-level quantification of nitrosamine impurities (NDEA, NDIPA, NEIPA, NMBA, NMPA, NDMA and NDBA) in Favipiravir API. The set of nitrosamine impurities were separated on gradient elution mode (1.0%v/v formic acid and 100.0% methanol) throughout a 20 min run period using Symmetry C18 (150X4.6 mm, 5 µm) with a flow rate of 0.8 mL/min. The Column oven was saturated to attain a temperature of 40º±1.0ºC, where the auto sampler was maintained at 5 . A rinse volume of 1200 µL was employed before and after aspiration, with a dip time of 5 seconds. All the nitrosamine impurities were quantified and ionized in positive polarity mode of Electron Spray Ionization (ESI) using Multiple Reaction Monitoring (MRM).Results: The retention times of the impurities NDEA, NDIPA, NEIPA, NMBA, NMPA, NDMA, NDBA and Favipiravir were found to be 8.51, 10.54, 9.60, 6.45, 11.06, 5.41, 12.67 and 6.96 min respectively. % Individual impurity in un spiked test solution has not been detected with any of the impurities. 1.29-1.98 was the %RSD for precision with 6-time repetitions Linearity was tested for specific impurities at six levels (5-100 ng/mL), with correlation coefficients (r2 ) ranging from 0.995-0.999. The percentage recovery of each impurity at LOQ level was observed to be 83.7-107.2, whereas 91.1-101.8 at three levels of accuracy (50%, 100%, 200%) injected in triplicate.Conclusion: This novel LC-MS/ MS method effectively separates and quantifies seven nitrosamine impurities in Favipiravir API, offering a reliable tool for quality control. This study validates an LC-MS/MS method for detecting nitrosamine impurities in Favipiravir API according to International Conference on Harmonization (ICH) guidelines
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Remidicherla, S. S., Chakravarthi, G., Malothu, N., & Reddy, A. R. (2025). A Comprehensive LC-MS/MS Method for Detecting Genotoxic Nitrosamine Impurities in Favipiravir API. Indian Journal of Pharmaceutical Education and Research, 59(1s), s256-s263. https://doi.org/10.5530/ijper.20250167
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