An update on latest regulatory guidelines and analytical methodologies for N-nitrosamine impurities in pharmaceutical products – 2024

Manchuri, Krishna Moorthy1,*; Kuril, Akhilesh Kumar2; Shaik, Mahammad Ali1; Gopireddy, Venkata Subba Reddy1; Sultana, Naziya1

Author Information

1Department of Chemistry, Jawaharlal Nehru Technological University Anantapur, Ananthapuramu, Andhra Pradesh, India

2Department of Pharmacy, Bhagwant University, Ajmer, Rajasthan, India

*Correspondence to: Krishna Moorthy Manchuri, PhD, krishna.manchuri@gmail.com.

Abstract

Controlling or eliminating N-nitrosamine impurities in pharmaceutical products has become a significant challenge for both drug manufacturers and regulatory authorities. This difficulty is particularly pronounced in light of the recent increase in nitrosamine drug substance-related impurities, which have raised concerns about the safety and efficacy of various medications. Additionally, the pharmaceutical industry faces the challenge of developing analytical methods that are not only sensitive and selective but also precise and accurate. These methods are crucial for the reliable quantification of low levels of N-nitrosamine impurities, ensuring compliance with stringent current regulatory guidelines. The intricate nature of detecting these impurities at such low levels necessitates the use of cutting-edge analytical techniques, such as liquid chromatography-mass spectrometry and gas chromatography-mass spectrometry. In light of these challenges, this review article explores the latest regulatory guidelines and analytical methodologies concerning N-nitrosamine impurities in various pharmaceutical products for 2024. Findings from this review article help provide valuable insights for researchers and industry professionals to enhance the safety and quality of pharmaceutical products.

摘要

控制或消除药品中的N-亚硝胺杂质已成为制药企业和监管机构共同面临的重大挑战。随着近期亚硝胺类原料药相关杂质的检出频次增加，这一难题愈发凸显——这些杂质已引发人们对多款药物安全性与有效性的担忧。此外，制药行业还面临分析方法开发的挑战：所建立的方法不仅需要具备高灵敏度与选择性，更要保证精密度和准确性。这些方法对于可靠定量分析痕量N-亚硝胺杂质、确保符合现行严格监管要求至关重要。由于痕量检测的复杂性，必须采用液相色谱-质谱联用、气相色谱-质谱联用等尖端分析技术。基于上述挑战，本综述探讨了2024年各类药品中N-亚硝胺杂质的最新监管指南及分析检测方法。研究成果将为研究人员和行业从业者提供宝贵见解，助力提升药品安全性与质量水平。