Analytics and spectra · Impurities
“A peak has appeared above the identification threshold, and we do not know what it is.”
Identify an unknown impurity by LC-MS
An unknown peak above the identification threshold holds up release, a stability study or a submission. CovaSyn interprets your LC-MS data and, where available, NMR data, proposes structures that fit the API and the process, and then classifies them toxicologically. Your expert reviews and signs off the report.
Starting point
When you need this
- A new peak appears in the stability study or after a process change.
- The impurity profile of a generic differs from the reference product.
- Mass balance does not close in forced degradation, and degradation products are missing.
- The authority asks for the structure and classification of an impurity so far only listed by relative retention time.
Result
What you get
Structure candidates with reasoning
Molecular formula from accurate mass and isotope pattern, fragment annotation and a ranked list of plausible structures derived from API, synthesis route and degradation pathways.
Impurity profile and mass balance
Assignment of peaks to process impurities or degradation products and a check whether the mass balance of the stressed samples closes plausibly.
ICH M7 classification
For each candidate, structural alerts, a mutagenicity prediction with applicability domain and a proposed ICH M7 class.
Report for sign-off
Data, conclusions and open points are in the report, including the measurement that would finally confirm a structure.
Three ways
Yourself, together, or done for you
Run it yourself
Draw the molecule in the sketcher or use the tools through the CovaSyn MCP directly in Claude, ChatGPT or Cursor.
Go to MCPLearn it together
In a workshop your team learns how to answer questions like this with AI, cleanly and traceably.
See workshopsDone for you
We run the evaluation with our tools and deliver the finished report. Your expert reviews and signs off.
See Done-for-You
CovaSyn
The tools behind it
Deterministic calculations instead of guessed answers: the same tools we use for Done-for-You work are available to you directly.
Covams
Unknown peak analysis, molecular formula, isotope pattern, fragment annotation and neutral losses, impurity profiling, degradation product prediction, forced degradation and mass balance.
Covanmr
Structure confirmation from NMR data of an isolated or enriched fraction, candidate verification and impurity analysis.
Covatox
ICH M7 classification, structural alerts, applicability domain check and comparison with similar structures that have already been assessed.
Audience
Who it is for
For analytical, CMC and regulatory affairs teams at contract labs, CDMOs and generics manufacturers, wherever an unknown impurity holds up a release or a submission.
What the computation does not replace
- Mass spectrometry alone often cannot distinguish positional isomers. A structure only counts as confirmed once NMR data or a reference standard support it.
- ICH M7 classification is based on predictions and needs review by a qualified expert; we state explicitly when a structure lies outside the applicability domain.
- A prediction does not replace a measurement. Without fragment spectra or accurate masses the conclusion stays correspondingly preliminary.
Insights
Read on
Unknown Impurity Identification by LC-MS/MS
Unknown impurity identification by LC-MS: formula from accurate mass, RDBE, isotope pattern and MS/MS fragment logic, with real CovaMS tool output and its.
Read articleMass Balance in Forced Degradation, and Why It Fails
Why mass balance in forced degradation rarely closes: non-chromophoric and volatile degradants, adsorption and response factors, plus how to close the gap.
Read articleForced Degradation Study Design (ICH Q1A R2)
Forced degradation study design under ICH Q1A(R2): stressor choice, target degradation, mass balance and stability-indicating methods, with real tool output.
Read articleICH M7 Classification: Class 1 to 5, by Example
ICH M7 classification explained class by class, with the dual (Q)SAR assessment and five real impurities scored live by CovaTox, including NDMA.
Read articleNitrosamine Risk Assessment: An ICH M7 Workflow
A practical nitrosamine risk assessment workflow for NDSRIs: ICH M7 dual assessment, real CovaTox classifications, and where the QSAR goes out of domain.
Read article
Questions
Common questions
How do I identify an unknown impurity by LC-MS?
First determine the molecular formula from accurate mass and isotope pattern, then derive fragments and neutral losses from the MS/MS spectrum and match them against the API, the synthesis route and known degradation pathways. CovaSyn works through these steps systematically and delivers a ranked list of candidates with reasoning.
Who can identify an unknown impurity for us?
CovaSyn does this as Done-for-You: you describe the peak, substance and data in the intro call, we agree on scope, and you typically receive the report within 5 working days once we have your data. Handled confidentially from the start.
When does an impurity have to be identified?
For drug substances and drug products, ICH Q3A and Q3B set reporting, identification and qualification thresholds that depend on the maximum daily dose. Potentially mutagenic impurities additionally fall under ICH M7 with much lower limits. CovaSyn supports identification and classification; which threshold applies to your product is decided by your regulatory expert.
What should I do if mass balance does not close in forced degradation?
Common causes are degradation products without a chromophore, volatile or non-eluting products and different response factors. CovaSyn predicts likely degradation products, searches for them in your MS data and shows where the missing mass most likely is.
How is an identified impurity classified under ICH M7?
The structure is checked for mutagenicity alerts and assessed with two complementary prediction methodologies, followed by expert review. Covatox provides alerts, prediction and applicability domain as the basis; your qualified expert signs off the classification.
Can I run this analysis myself?
Yes. In the sketcher you draw candidate structures and see core data instantly; the MS, NMR and toxicology tools are available through the CovaSyn MCP directly in your AI assistant.
Analytics and spectra
Related problems we solve
Next step
Tell us about your unknown peak.
30 minutes on Microsoft Teams with the CovaSyn team. If it is not a fit, we will say so.