# Determination of nitrite in rifapentine and analysis of the formation causes of nitrosamine impurity

## 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.

## Key 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 experimental results. This IC analytical method has the dual applications of genotoxic impurity quality control and elucidating impurity formation pathways in small-molecule drugs.