Patheon: End-to-end pharma services solutions for every drug development journey

Significance of the Topic

The presence of nitrosamine impurities in pharmaceutical products poses a serious genotoxic and carcinogenic risk to patients. Regulatory authorities such as the FDA and EMA mandate strict monitoring and control of these alkylating agents to ensure patient safety and drug efficacy. Robust analytical strategies are essential to detect nitrosamines at trace levels and to support regulatory approval and market access.

Objectives and Study Overview

This case study describes Patheon’s collaboration with clients to develop fit-for-purpose nitrosamine testing methods. Focusing on a ranitidine drug product example, the goal was to optimize methodologies based on FDA recommendations and in-house expertise, leveraging both high-resolution accurate mass (HRAM) spectrometry and triple quadrupole (QqQ) instruments.

Methodology and Instrumentation

Method development began by evaluating published QqQ and HRAM protocols. The team iteratively adjusted chromatographic and mass spectrometric parameters to achieve required sensitivity and specificity. Ongoing dialogue with clients guided method optimization and validation under GMP conditions.

Used Instrumentation

• Thermo Scientific TSQ Fortis and TSQ Fortis Plus triple quadrupole mass spectrometers
• High-resolution accurate mass spectrometer
• Thermo Scientific Chromeleon Chromatography Data System (CDS)

Key Results and Discussion

The TSQ Fortis series delivered robust performance, excellent linearity, and detection limits meeting published nitrosamine thresholds. Simplified maintenance—including ion source cleaning without breaking vacuum—ensured minimal downtime and reliable day-to-day operation. Chromeleon CDS facilitated user-friendly data processing and comprehensive audit trails, satisfying regulatory documentation requirements.

Benefits and Practical Applications

Patheon’s integrated manufacturing and analytical capabilities enable a one-stop-shop approach, reducing client workload and accelerating development timelines. Fit-for-purpose methods support registration dossiers and routine quality control, ensuring safe drug supply.

Future Trends and Opportunities

As regulatory scrutiny on nitrosamines and other impurity classes intensifies, dedicated analytical platforms will become more prevalent. Emerging technologies such as automated workflows, AI-driven data analysis, and enhanced mass spectrometry platforms promise further improvements in sensitivity, throughput, and compliance.

Conclusion

Through client collaboration, methodical optimization, and strategic use of robust instrumentation, Patheon delivers validated nitrosamine testing solutions that satisfy regulatory requirements and safeguard patient health.