Introduction: Why Proactive Nitrosamine Testing is Critical in 2025
In 2025, regulatory scrutiny around nitrosamine contamination in pharmaceutical products continues to intensify. With multiple FDA and EMA recalls already issued this year, pharmaceutical companies are increasingly turning to proactive nitrosamine testing to ensure compliance, product integrity, and patient safety. In this case study, we explore how a U.S.-based mid-size pharmaceutical company partnered with ResolveMass Laboratories Inc. to conduct proactive nitrosamine testing, successfully identifying and mitigating nitrosamine risks before submitting their NDA, ultimately preventing potential recalls and regulatory setbacks.
👉 ResolveMass Laboratories offers comprehensive Nitrosamine Analysis and confirmatory testing solutions, making it a trusted CRO partner for forward-thinking pharmaceutical developers.
Background: The Challenge
The client, a mid-sized U.S. pharmaceutical firm, was preparing to file an NDA for a small-molecule cardiovascular drug. Internal R&D flagged the possibility of nitrosamine impurities forming during synthesis. With increasing global regulatory focus on NDSRIs (Nitrosamine Drug Substance-Related Impurities), they required an experienced partner to:
- Proactively assess nitrosamine risks.
- Perform in-depth analytical testing.
- Guide mitigation strategies.
They chose ResolveMass Laboratories for our demonstrated expertise in proactive nitrosamine testing and risk assessment strategies aligned with the latest FDA and ICH M7 guidelines.
Step 1: Risk Assessment and Structural Evaluation
Our scientific team initiated a comprehensive nitrosamine risk assessment to determine potential formation pathways. We evaluated:
- API and excipient structures
- Synthetic route and reagents
- Packaging materials
- Environmental and storage conditions
This phase was guided by our proprietary predictive risk engine developed specifically for proactive nitrosamine testing, with strong alignment to the latest guidance from global health authorities.
Proactive nitrosamine testing begins not in the lab, but with deep structural analysis and synthesis route scrutiny.
Step 2: In-Silico & In-Vitro Nitrosamine Profiling
To narrow down the potential NDSRI candidates, we employed:
- In-silico prediction models
- Ames test simulation
- Mass spectral fragment library screening
We identified two probable NDSRIs that could arise as low-level byproducts in specific reaction steps. These were synthesized and validated against client batch samples using LC-MS/MS and GC-MS.
This proactive approach is why pharmaceutical companies choose ResolveMass Laboratories Inc. for their proactive nitrosamine testing needs.
👉 Explore our analytical capabilities at Nitrosamine Analysis Services
Step 3: Analytical Method Development & Validation
Our method development team built a validated LC-MS/MS method with the following features:
- LOQ: 5 ppb for key nitrosamines
- Selective detection of NDSRIs in complex matrices
- Robust against interference from excipients
The developed method adhered to both USP <1469> and ICH Q2(R2) guidelines. Validation included:
- Linearity, accuracy, precision
- Specificity
- Matrix effects
These high-sensitivity assays are foundational to our proactive nitrosamine testing workflows.
Step 4: Batch Analysis and Mitigation Guidance
Upon testing three batches of the drug substance and final formulation:
- Trace levels of NDSRI were detected (4–6 ppb)
- These were below the interim AI (acceptable intake) levels
- However, further mitigation was recommended to eliminate risk
We provided actionable guidance:
- Replacing nitrosating reagents with safer alternatives
- Optimizing purification steps
- Reevaluating packaging leachables
Our consultative and scientific approach reinforces our value as a leading proactive nitrosamine testing CRO.
Outcome: Successful Submission Without Delay
Thanks to our early intervention, the client:
- Prevented downstream regulatory delays
- Gained confidence in their NDA submission
- Avoided costly recalls and reputation damage
ResolveMass Laboratories’ proactive nitrosamine testing program became a core part of the client’s ongoing risk management SOPs.
“ResolveMass didn’t just test our product—they helped us understand and mitigate risk at the molecular level. Their proactive nitrosamine testing program gave us a true regulatory advantage.” — Director, Regulatory Affairs (Client Testimonial)
Why ResolveMass for Proactive Nitrosamine Testing?
At ResolveMass Laboratories Inc., we bring deep scientific expertise in:
- Synthesis of NDSRI reference standards
- Ultra-trace quantification via LC-MS/MS
- In-silico impurity prediction
- Full regulatory documentation support
👉 Explore how we can support your drug development at Nitrosamine Testing Services
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Conclusion: The ROI of Proactive Nitrosamine Testing
In an era of heightened regulatory expectations, proactive nitrosamine testing is no longer optional—it’s a strategic imperative. This case study illustrates how forward-thinking drug developers can prevent compliance issues by engaging experienced partners like ResolveMass Laboratories Inc.
If you’re developing a drug product or preparing for regulatory submission, now is the time to invest in proactive nitrosamine testing.
Let ResolveMass help you stay ahead of the curve.
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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 United States and 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 PhD level scientists who has specialized experience in Mass Spectrometry and Nitrosamine Impurity chemistry.
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. We also provide the custom synthesis service of rare nitrosamine Impurities which are not available anywhere.
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 transparent nitrosamine testing services in United States and Canada—where precision meets reliability.
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References
- EMA. (2021). Assessment and Mitigation of Nitrosamine Risk in Human Medicines. https://www.ema.europa.eu/en/documents/referral/nitrosamines-emea-h-a53-1490-assessment-report_en.pdf
- FDA. (2021). Control of Nitrosamine Impurities in Human Drugs. https://www.fda.gov/media/141720/download
- Health Canada. (2020). Guidance on Nitrosamine Impurities in Medications. https://www.canada.ca/en/health-canada/services/drugs-health-products.html
- ICH. (2023). ICH M7(R2) – Control of Mutagenic Impurities. https://database.ich.org/sites/default/files/M7_R2_Guideline_Step4_2023_0223.pdf
