What Are Nitrosamines?

Nitrosamines, a broad class of N-nitroso compounds, have been linked to serious health risks, including cancer. These compounds are often found in pharmaceuticals, leading to heightened concerns over safety.

The Challenge of Detection

Detecting nitrosamines at acceptable levels poses a significant challenge for the pharmaceutical industry. Gathering safety data for these impurities is often difficult, making it hard to establish acceptable intake limits. In the absence of direct data, scientists may turn to structurally similar compounds for guidance—if they're available.

A Roundtable of Experts Tackles the Issue

To confront these complex challenges, leading experts recently gathered at LCGC International for a peer exchange. Moderated by Aloka Srinivasan of Raaha, the panel featured Mayank Bhanti from the United States Pharmacopeia (USP) and Amber Burch from Purisys. Together, they explored the multifaceted problems surrounding nitrosamine analysis.

Key Analytical Hurdles

Bhanti outlined the five primary analytical challenges in nitrosamine detection. Regulatory agencies now require unprecedentedly low sensitivity levels, necessitating advanced techniques like liquid chromatography-tandem mass spectrometry (LC-MS/MS). However, achieving robustness and reproducibility in detecting these low levels can still be tricky.

"The interferences we face, particularly with mass spectrometry, can skew our results," Bhanti explained, pointing out that ion sources could potentially underestimate nitrosamine levels.

Precision is Key

Sample preparation also plays a critical role. Optimizing extraction and cleanup processes becomes vital to achieving the required sensitivity. An even tougher challenge arises with nitrosamine drug substance-related impurities, which can emerge during drug synthesis or storage.

Bhanti advocates for the adoption of higher-resolution technologies, like high-resolution mass spectrometers (HRMS), to improve analysis accuracy.

Burch emphasized the necessity for consistent precision across different labs and analysts. "It's crucial that methods can be executed accurately anywhere to ensure the longevity of products," she said.

The Road Ahead

As regulatory requirements evolve, pharmaceutical companies must remain agile in their approaches to nitrosamine detection. A comprehensive strategy is essential to overcome these challenges and ensure the safety of drugs reaching patients.

The conversation among these experts highlights the ongoing battle against nitrosamine impurities in pharmaceuticals, underscoring a commitment to safeguarding public health.