Nitrosamine Impurities in Pharmaceuticals: How LabSense Ensures Safety and Compliance

Why Nitrosamines Matter

Nitrosamines are a class of chemical compounds that have raised significant concern in the pharmaceutical industry due to their carcinogenic potential. Since 2018, when nitrosamine impurities such as NDMA and NDEA were first detected in certain sartan medicines, regulators including the European Medicines Agency (EMA) and the U.S. Food and Drug Administration (FDA) have introduced strict acceptable intake (AI) limits.

These findings highlighted the urgent need for sensitive, validated analytical methods capable of detecting nitrosamines at trace levels in both active pharmaceutical ingredients (APIs) and finished products.

Sources of Nitrosamine Impurities

Nitrosamines can be introduced into pharmaceutical products through different pathways, typically divided into two main groups:

1. Solvent- and reagent-related nitrosamines
   Formed when secondary or tertiary amines (e.g., dimethylamine, diethylamine) present in solvents or reagents react with nitrosating agents.
   Examples include NDMA, NDEA, NEIPA, and NDIPA.

2. API-related nitrosamines (NDSRIs – Nitrosamine Drug Substance-Related Impurities)
   Formed when the structure of the API or its intermediates contains vulnerable amine groups that can undergo nitrosation.
   These are often compound‑specific and require tailored analytical strategies.

Both groups present challenges for manufacturers and demand robust testing strategies to ensure compliance and protect patient health.

Regulatory Expectations

Regulators worldwide require:

• Risk assessment of all potential nitrosamine formation pathways.
• Analytical testing of APIs, intermediates, and finished products using validated, sensitive methods.
• Ongoing monitoring to ensure continued compliance with AI limits set by EMA, FDA, and other agencies.

LabSense Capabilities in Nitrosamine Detection

At LabSense, we have developed advanced analytical workflows specifically designed to detect and quantify nitrosamine impurities:

• LC‑MS/MS equipped with APCI and ESI ionization

  • Allows ultra‑sensitive detection of a broad range of nitrosamines.
  • Flexibility in ionization improves coverage for structurally diverse compounds.

• GC‑MS/MS methodologies

  • Provide additional specificity and serve as confirmatory techniques for volatile nitrosamines.

• Validated methods aligned with EMA/FDA guidance

  • Cover both solvent‑related nitrosamines and API‑related NDSRIs.
  • Applied across APIs, raw materials, intermediates, and final dosage forms.

Our services are designed to support pharmaceutical companies in meeting regulatory expectations, ensuring market compliance, and, above all, protecting patient safety.

Why Partner with LabSense?

• Expertise in regulatory compliance – We stay aligned with EMA/FDA updates and guidance.
• State‑of‑the‑art instrumentation – Sensitive LC‑MS/MS with APCI/ESI and confirmatory GC‑MS/MS.
• Comprehensive testing scope – Covering both groups of nitrosamines, from solvents to API‑related impurities.
• Reliable results – Validated methods and expert interpretation for confident decision‑making.

Conclusion

Nitrosamine testing is no longer optional – it is a regulatory and patient safety requirement. With its specialized capabilities, LabSense provides pharmaceutical manufacturers with the tools and expertise needed to detect, quantify, and control nitrosamine impurities.