Determination of nitrite in rifapentine and analysis of the formation causes of nitrosamine impurity
Yaodong Ping, Yongxiang Liu, Hairuo Wen, Nie Wen, Bin Li, Yuan Chen, Ye Tian
TL;DR
This paper presents a new method to detect and analyze nitrosamine impurities in rifapentine, a drug, to improve safety and understand how these harmful substances form.
Contribution
A novel valve-switching ion chromatography method is developed for detecting nitrosamine impurities and validating their formation pathway in rifapentine.
Findings
The developed IC method shows good linearity, accuracy, and detection limits for nitrosamine analysis.
Nitrification experiments confirm that CPNP in rifapentine is formed via a nitrosation pathway.
The method can be used for both quality control and understanding impurity formation in drugs.
Abstract
During drug manufacturing, residual nitrosamine salts in the final formulation are a key contributor to the formation of genotoxic nitrosamine impurities. However, trace-level concentrations and strong matrix interference complicate nitrosamine salt detection; therefore, selecting an appropriate analytical method is crucial. We developed a valve-switching ion chromatography method and performed method validation. We also conducted nitrification degradation experiments and validation studies of the nitrification pathway by detecting 14N-CPNP and 15N-CPNP using LC-HRMS after adding 15N-nitrite to rifaentine. The results of the method validation indicate its good linearity, accuracy, quantification, and detection limits. Nitrification degradation experiments demonstrate that CPNP in rifapentine can be generated via a nitrosation pathway. This pathway has also been validated by…
Genes, proteins, chemicals, diseases, species, mutations and cell lines named across the full text — each resolved to its canonical identifier and authoritative record.
Click any figure to enlarge with its caption.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9Peer Reviews
No public reviews on file for this paper yet. If you reviewed it on a platform where reviews are public (OpenReview, ICLR, NeurIPS, ICML), you can paste yours below so the community can read it here.
Videos
No videos yet. Explain this paper in a talk, walkthrough, or lecture? Add one.
Taxonomy
TopicsWater Treatment and Disinfection · Carcinogens and Genotoxicity Assessment · Sulfur Compounds in Biology