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Risk Assessment
Structured evaluation of formation and carry-over risk across API, excipients, process and packaging.
All services
Specialised Capability · Testing & Stability
Nitrosamine Impurity Testing for regulatory confidence.
Stabicon operates a dedicated nitrosamine testing capability covering risk assessment, ultra-trace quantitation and confirmatory analysis of N-nitrosamine impurities – including small-molecule nitrosamines (NDMA, NDEA) and complex Nitrosamine Drug Substance-Related Impurities (NDSRIs).
Our methods are developed and validated to detect impurities at parts-per-billion (ppb) to parts-per-trillion (ppt) levels using LC-MS/MS and GC-MS/MS, with workflows aligned to ICH M7(R2), US FDA and EMA expectations.
Quick Capability Overview
Ultra-trace nitrosamine analysis across the full impurity lifecycle.
Capability
Scope
- Regulatory AlignmentICH M7(R2), US FDA, EMA, CDSCO guidance
- AnalytesNDMA, NDEA, NMBA, NDIPA, NDBA, NMPA, NDPA + NDSRIs
- TechniquesLC-MS/MS, GC-MS/MS, GC-HRMS, headspace GC-MS
- SensitivityQuantitation at ppb to ppt levels
- MatricesAPIs, drug products, excipients, packaging & water
- Risk Assessment3-step evaluation, confirmatory & mitigation support
- Limit SettingAcceptable Intake (AI) determination per ICH M7
- DeliverablesValidated methods, COAs & regulatory-ready reports
Why Nitrosamine Control Matters
Nitrosamines are potent, highly regulated genotoxic impurities.
Following global recalls of sartans, ranitidine and metformin, regulators now require manufacturers to evaluate every drug substance and drug product for the potential presence of N-nitrosamine impurities and to control them below strict acceptable-intake limits.
Because nitrosamines can form from secondary or tertiary amines reacting with nitrosating agents – in the API, excipients, packaging or even during storage – control requires both a structured risk assessment and analytical methods sensitive enough to detect impurities at trace levels.
Stabicon supports manufacturers across the complete nitrosamine control workflow: structured risk evaluation, sensitive confirmatory testing, NDSRI characterisation and mitigation strategy – generating data that withstands regulatory scrutiny.
Our Nitrosamine Capabilities
A complete nitrosamine programme – assessment to confirmation.
We perform a structured risk evaluation across the API synthetic route, excipients, water, recovered solvents, packaging and manufacturing process to determine whether nitrosamines could plausibly form or carry over.
Assessment covers
- Route-of-synthesis and reagent review
- Excipient and packaging interaction risk
- Cross-contamination and carry-over risk
- Degradation and storage-induced formation
- NDSRI predisposition for amine-containing APIs
Frameworks
ICH M7(R2)US FDA guidanceEMA Q&ACDSCO
Where risk is identified, we deploy validated, highly sensitive methods to confirm presence and quantify nitrosamines at the trace levels required by regulators.
Analytical platforms
- LC-MS/MS (triple-quadrupole)
- GC-MS/MS and headspace GC-MS
- High-resolution MS (HRMS) confirmation
- Matrix-matched calibration & recovery studies
Targets
NDMANDEANMBANDIPANDBANMPANDPA
Nitrosamine Drug Substance-Related Impurities are API-specific and often lack ready reference standards. We support method development, characterisation and predicted-limit setting for NDSRIs.
Support includes
- API-specific NDSRI method development
- Reference standard sourcing / characterisation
- Enhanced Ames test & SAR-informed limit context
- Carcinogenic potency category (CPCA) alignment
Approach
Compound-specific AIRead-acrossCPCA framework
We develop and validate sensitive, selective and robust methods specific to your product and matrix, validated for use in release and stability testing.
Validation parameters
- Specificity and selectivity
- LOD / LOQ at required AI limits
- Linearity, accuracy and precision
- Recovery, robustness and stability of solutions
Standards
ICH Q2(R1)ICH M7(R2)Pharmacopeial
We help establish acceptable intake limits and convert them into product-specific concentration limits based on maximum daily dose, supporting compliant specifications.
Includes
- AI limit assignment per ICH M7(R2)
- Maximum-daily-dose-based limit conversion
- Total nitrosamine and multiple-impurity control
- Specification justification for filings
Outputs
AI limitsConcentration limitsSpecifications
Every programme is delivered with traceable, submission-ready documentation to support your regulatory responses and dossiers.
Deliverables
- Risk assessment reports
- Validated analytical methods & reports
- Certificates of Analysis (COAs)
- Regulatory response and dossier support
Compliance
Data integrityTraceabilitycGMPNABL
Products & Matrices We Support
Broad category expertise. Trace-level sensitivity..
Product Categories
Pharmaceuticals (APIs & finished dose)NutraceuticalsOTC ProductsHerbal & Natural ProductsExcipients & Raw Materials
Matrices Tested
Active pharmaceutical ingredientsTablets, capsules & liquidsExcipients & solventsPrimary packaging materialsPurified & process water
Instrumentation & Scientific Capability
Mass-spectrometry infrastructure built for trace detection.
Our nitrosamine programmes run on qualified, high-sensitivity mass-spectrometry platforms within a cGMP, NABL-accredited quality framework.
Analytical Platforms
- LC-MS/MS triple-quadrupole systems
- GC-MS/MS and headspace GC-MS
- High-resolution MS confirmation
- Qualified, calibrated instrumentation
- Controlled reference-standard handling
Integrated Support
Nitrosamine testing is integrated with our wider testing centre:
- Analytical Research & Development
- Method Validation
- Stability testing & storage
- Quality Control release testing
This allows seamless execution from risk assessment through confirmatory testing and stability monitoring.
Regulatory & Quality Compliance
Programmes aligned to global nitrosamine guidance.
Every nitrosamine programme is executed within a structured quality framework designed for audit readiness and regulatory reliability.
Guidance Frameworks
- ICH M7(R2)
- US FDA nitrosamine guidance
- EMA nitrosamine Q&A
- CDSCO directives
- CPCA / enhanced Ames context
Documentation Support
- Risk assessment reports
- Validation protocols & reports
- COAs and trend data
- Regulatory response support
- Investigation reports
Our Nitrosamine Workflow
A structured, three-step control approach.
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Method Development
Fit-for-purpose LC-MS/MS or GC-MS/MS method development for the specific analyte and matrix.
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Validation
Validation to ICH M7 / Q2 at the sensitivity required by the acceptable intake limit.
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Confirmatory Testing
Ultra-trace quantitation and confirmation against established limits.
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Limit Setting
Acceptable Intake and product-specific concentration limit determination.
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Reporting & Support
Submission-ready documentation and ongoing stability monitoring.
Why Stabicon
Nitrosamine expertise backed by scientific integration.
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Dedicated MS Capability
High-sensitivity LC-MS/MS and GC-MS/MS platforms for ppb–ppt detection.
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End-to-End Workflow
From structured risk assessment through confirmatory testing and limit setting.
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NDSRI Competence
Support for complex, API-specific drug substance-related nitrosamine impurities.
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Regulatory Alignment
Methods and reports aligned to ICH M7(R2), US FDA and EMA expectations.
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Integrated Stability
Nitrosamine monitoring built into ICH stability programmes.
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Audit-Ready Documentation
Traceable, data-integrity-compliant reporting for filings and responses.
Frequently Asked Questions
Common nitrosamine questions.
We test for small-molecule nitrosamines such as NDMA, NDEA, NMBA, NDIPA, NDBA, NMPA and NDPA, as well as API-specific Nitrosamine Drug Substance-Related Impurities (NDSRIs).
Using LC-MS/MS and GC-MS/MS, our validated methods quantify nitrosamines at parts-per-billion to parts-per-trillion levels, in line with acceptable intake limits.
Yes. We support the full three-step approach – structured risk assessment, confirmatory testing and mitigation/limit-setting – aligned to ICH M7(R2), US FDA and EMA guidance.
Yes. We support NDSRI method development, reference-standard sourcing or characterisation, and limit setting using compound-specific AI, read-across and CPCA frameworks.
Yes. Nitrosamine monitoring can be built into ICH stability programmes so formation over shelf-life is tracked and documented.
Related Programs
All services Often paired with this service.
Partners typically bundle these capabilities into a single timeline-driven engagement. Combine programs to reduce filing risk and accelerate market readiness.
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Analytical Research & Development
Method development for assay, related substances, dissolution and impurity profiling – calibrated against pharmacopeial monographs.
Explore02
Stability Study
ICH-compliant stability programs across all climatic zones – long-term, accelerated and stress conditions for rigorous shelf-life determination.
Explore03
Method Validation
Validation packages aligned to ICH Q2(R1) and USP <1225> – fully documented for global filings and tech transfer.
ExploreHero ingredients we routinely put through this service.
Nitrosamine Testing
Control nitrosamines with trace-level certainty.
Whether you need a risk assessment, a validated confirmatory method or ongoing nitrosamine monitoring on stability, Stabicon delivers regulatory-ready nitrosamine testing for pharma, nutraceutical and natural-product manufacturers.