Nitrosamine Testing for API Manufacturers in Canada: Why It’s Non-Negotiable

Introduction

Over the past few years, Nitrosamine Testing for API Manufacturers in Canada has moved from being a regulatory formality to a fundamental pillar of pharmaceutical quality assurance. Nitrosamines—classified as probable human carcinogens by global regulatory bodies such as Health Canada, the EMA, and the US FDA—have raised serious safety concerns across the pharmaceutical landscape. Their unexpected presence in active pharmaceutical ingredients (APIs) has triggered international recalls, supply chain disruptions, and a renewed focus on impurity control strategies.

For Canadian API manufacturers, this isn’t just about checking a compliance box—it’s about proactively safeguarding public health, product integrity, and market trust.

At ResolveMass Laboratories Inc., we understand the scientific and regulatory complexity behind nitrosamine testing. As a trusted Canadian Contract Research Organization (CRO), we’ve built our analytical workflows to meet the most stringent global standards. Our team of seasoned scientists, combined with cutting-edge LC-MS/MS and HRMS instrumentation, offers end-to-end support—from risk assessment and method development to routine monitoring and regulatory submissions.

In this blog, we’ll explore why nitrosamine testing is non-negotiable, how it’s evolving in the Canadian regulatory context, and what actionable steps manufacturers can take to stay ahead—both scientifically and strategically.

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What are Nitrosamines?

Nitrosamines are a class of chemical compounds that can form unintentionally under specific manufacturing conditions—most commonly when secondary or tertiary amines interact with nitrosating agents like nitrites in the presence of heat, moisture, or acidic environments. In the context of pharmaceutical manufacturing, this can occur during synthesis, storage, or even packaging of Active Pharmaceutical Ingredients (APIs) and finished drug products.

While these compounds may seem like trace-level impurities, their impact is far from negligible. Several nitrosamines, including N-Nitrosodimethylamine (NDMA) and N-Nitrosodiethylamine (NDEA), are recognized as probable human carcinogens by the International Agency for Research on Cancer (IARC). Even minute concentrations—measured in parts per billion (ppb)—can pose a long-term health risk with chronic exposure.

Why is Nitrosamine Testing for API Manufacturers in Canada Mandatory?

1. Regulatory Compliance and Enforcement

Health Canada mandates strict compliance with nitrosamine limits in pharmaceuticals. In fact, failure to comply has led to multiple recalls in the Canadian market. Regulatory bodies expect API manufacturers to identify risk factors, perform confirmatory testing, and implement control strategies to limit nitrosamine formation.

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2. Patient Safety and Public Health

Contaminated APIs can compromise patient safety, potentially leading to chronic exposure to carcinogenic substances. Ensuring the absence or acceptable levels of nitrosamines through rigorous testing is a moral, scientific, and regulatory necessity.

Canadian Regulations and Global Harmonization

Health Canada’s approach to nitrosamine control aligns with international agencies like the EMA and US FDA. Manufacturers must submit risk assessments and confirmatory testing data. These guidelines demand method development, validation, and sensitive quantification of nitrosamines.

Analytical Techniques for Nitrosamine Testing

ResolveMass Laboratories employs highly sensitive and validated analytical methods:

• LC-MS/MS (Liquid Chromatography-Tandem Mass Spectrometry)
• GC-MS (Gas Chromatography-Mass Spectrometry)
• HRMS (High-Resolution Mass Spectrometry)

These methods allow detection at ppb (parts per billion) levels and ensure robust quantification across complex API matrices.

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Real-Time Case Study: API Manufacturer Facing Market Recall

A Canadian API manufacturer faced a recall after NDMA contamination was detected in a blood pressure medication. Their internal testing failed to detect nitrosamines below 30 ppb, leading to regulatory action. They approached ResolveMass Laboratories for root cause analysis and re-validation of their test methods.

• Problem Identified: Nitrosamine formed due to nitrite-rich excipient reacting with residual amines.
• Solution Provided: ResolveMass deployed HRMS analysis, identified critical control points, and validated a mitigation strategy.
• Outcome: Manufacturer resumed supply within 8 weeks, now compliant with Health Canada regulations.

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Why Choose ResolveMass Laboratories for Nitrosamine Testing?

• Expertise: Our team comprises analytical chemists with 20+ years of cumulative experience in nitrosamine detection.
• Cutting-edge Infrastructure: We operate advanced LC-MS/MS and HRMS platforms validated under ICH and USP protocols.
• Speed & Accuracy: Industry-leading turnaround times without compromising data integrity.
• Regulatory Guidance: End-to-end support from risk assessment to Health Canada submission.

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Conclusion

Nitrosamine Testing for API Manufacturers in Canada is a non-negotiable obligation that upholds drug safety, regulatory compliance, and global market access. ResolveMass Laboratories empowers pharmaceutical partners to meet and exceed these standards with confidence. Don’t wait for regulatory recalls—proactively safeguard your manufacturing process.

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Top 10 FAQs on Nitrosamine Testing for API Manufacturers in Canada

1. What are nitrosamines and why are they dangerous?

Nitrosamines are impurities that can form in drug substances or products, particularly when secondary or tertiary amines react with nitrites. Many are classified as probable human carcinogens.

2. Is nitrosamine testing mandatory in Canada?

Yes. Health Canada mandates risk assessment and confirmatory testing for all drug products and APIs susceptible to nitrosamine formation.

3. Which nitrosamines are commonly tested?

Commonly tested include NDMA, NDEA, NMBA, NEIPA, and DIPNA, depending on the API and manufacturing process.

4. What detection levels are required?

The acceptable intake levels range from 26.5 to 96 ng/day, which translates to detection at ppb levels. Our lab detects even trace-level nitrosamines.

5. How often should manufacturers test for nitrosamines?

Testing should be conducted during initial validation, after significant changes, and routinely as per the risk assessment protocol.

6. Can nitrosamines be removed after formation?

Prevention is key. However, purification steps, process optimization, and excipient control can mitigate nitrosamine presence.

7. How do I know if my API is at risk?

ResolveMass Laboratories offers a structured risk assessment service, identifying all potential nitrosamine-forming pathways.

8. What analytical methods are used for nitrosamine testing?

We use LC-MS/MS, GC-MS, and HRMS methods, tailored to the specific sample matrix and regulatory requirement.

9. What turnaround time can I expect?

Typically within 5-10 business days, depending on sample complexity and batch size.

10. How can I initiate testing with ResolveMass?

Visit our Nitrosamine Testing page or reach out through our Contact Page for personalized consultation.

Relevant Pages for Further Exploration

• Nitrosamine Analysis Services
• Nitrosamine Detection Techniques
• Analytical Services for Pharmaceutical APIs
• High-Resolution Mass Spectrometry Services
• Nitrosamine Regulatory Updates Canada

ResolveMass Laboratories Inc.: Experience, Expertise, and Trust You Can Count On

ResolveMass Laboratories Inc. has established itself as a trusted name in the domain of nitrosamine testing services in Canada. With over a decade of dedicated experience, we have completed hundreds of successful nitrosamine testing and risk assessment projects for both domestic and international clients. Our scientists possess advanced degrees in analytical chemistry and pharmaceutical sciences, bringing a wealth of expertise to every project.

We are one of the few Canadian CROs to offer a complete in-house nitrosamine testing solution—from risk assessment to confirmatory analysis, regulatory documentation, and expert consultation. We continually invest in cutting-edge technologies and method development, keeping pace with evolving regulations and industry demands.

Our clients trust us because we not only deliver accurate results but also help them understand and resolve complex impurity challenges. Choose ResolveMass Laboratories for your nitrosamine testing services in Canada—where precision meets reliability.

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📞 Request a quote for method development
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1. Schmidtsdorff, M., et al. (2021). Recent advances in the analytical detection of nitrosamines in pharmaceuticals. Journal of Pharmaceutical and Biomedical Analysis, 204, 114270.https://doi.org/10.1016/j.jpba.2021.114270
2. Thompson, C. M., et al. (2020). Carcinogenic potential of N-nitrosamines: A review on structure-activity relationships. Critical Reviews in Toxicology, 50(8), 721–750.https://doi.org/10.1080/10408444.2020.1810551
3. Holzgrabe U. Nitrosated active pharmaceutical ingredients – lessons learned? J Pharm Sci. 2023;112(5):1210-5. doi:10.1016/j.xphs.2023.01.021. https://www.sciencedirect.com/science/article/abs/pii/S0022354923000230