PHARMA'S NITROSAMINE CHALLENGE: A REVIEW OF A CALL FOR VIGILANCE

Mostafa Essam Eissa

doi:10.22270/ujpr.v9i3.1119

Mostafa Essam Eissa Independent Researcher and Freelance Consultant, Cairo, Egypt.

10.22270/ujpr.v9i3.1119

Keywords:

Analytical methods, carcinogenic potential, nitrosamine impurities, pharmacopoeia, regulatory guidance, risk assessment and control

Abstract

Nitrosamines are potential carcinogens (cancer-causing agents) that can form in medications under specific conditions. The European Pharmacopoeia (EP) and the United States Pharmacopeia (USP) both set strict guidelines to minimize their presence. Nitrosamines form when nitrites and amines react in acidic environments, potentially occurring in the stomach or during drug production. They are classified as probable human carcinogens, meaning long-term exposure at high levels may increase cancer risk. Fortunately, nitrosamine levels in most medications are very low and unlikely to pose significant health risks. Both EP and USP have implemented a new general chapter: Nitrosamine Impurities (EP: 2.5.42 and USP: <1469>). These chapters outline acceptable intake limits for six specific nitrosamines and a four-step risk assessment and control strategy. They also detail testing procedures and analytical methods for detecting and measuring nitrosamines in medications. There are similarities between EP and USP as both set comparable acceptable intake limits for the same six nitrosamines. Also, both employ a similar four-step risk management approach. Moreover, both provide information on testing procedures and analytical methods. Nevertheless, there are few differences between both references. There may be slight variations in the specifics of analytical procedures (e.g., detection limits, chromatographic conditions). Regulatory agencies are actively monitoring and controlling nitrosamine levels in medications, ensuring patient safety. Both EP and USP play crucial roles in setting stringent standards and ensuring their consistent implementation across the pharmaceutical industry.