The practical answer
ICH Q3C groups residual solvents into Class 1 (to be avoided), Class 2 (to be limited, with ppm limits such as 410 ppm for acetonitrile) and Class 3 (low toxic potential, 0.5% without justification). ICH Q3D treats arsenic, cadmium, mercury and lead as Class 1 elements. Ask which solvents were used and how they were measured; a missing line is unresolved, not zero. [1] [2]
Evidence, method & source dates ↓Why these lines appear and what readers ask
Some peptide certificates include residual solvent or heavy-metal results, and many omit them. Buyers ask what "Class 2 below Option 1" means, whether a 0.5% loss on drying is acceptable, and whether a certificate without these lines is incomplete. The vocabulary comes from two ICH guidelines for pharmaceuticals.
Q3C states that it does not apply to drug substances or products used during clinical research stages of development, nor to existing marketed products, and Q3D likewise excludes products used during clinical research stages. [1] [2] Research-grade peptides are not shown to be bound by either guideline. Use them to understand a certificate's wording, not to assign a pass or fail.
Residual solvent classes in ICH Q3C(R9)
Q3C places solvents in three classes: Class 1 solvents to be avoided (known or strongly suspected human carcinogens and environmental hazards), Class 2 solvents to be limited, and Class 3 solvents with low toxic potential and permitted daily exposures of 50 mg or more per day. [1]
For Class 2, Option 1 concentration limits are calculated from the permitted daily exposure assuming a product mass of 10 g administered daily. Examples in Table 2 include acetonitrile at 410 ppm, dichloromethane at 600 ppm, N,N-dimethylformamide at 880 ppm and methanol at 3000 ppm. Class 3 solvents, such as acetic acid, acetone, ethanol and ethyl ether, are considered acceptable without justification at 50 mg per day or less, corresponding to 5000 ppm or 0.5% under Option 1. [1]
| Certificate wording | Q3C meaning | Follow-up question |
|---|---|---|
| "Only Class 3 solvents likely present; loss on drying < 0.5%" | An example supplier statement in Q3C section 3.5 [1] | Which solvents, and was the LOD method validated? |
| "Class 2 solvents X, Y below Option 1 limit" | Named Class 2 solvents below Table 2 ppm limits [1] | Which method and result for each named solvent? |
| A ppm result for one solvent | A measured value; compare to that solvent's Table 2 or Class 3 limit [1] | Does it cover every solvent used in the process? |
| No solvent line | Not addressed by the document | Ask; record as unresolved |
How solvents should be measured and reported
Q3C says residual solvents are typically determined by chromatographic techniques such as gas chromatography, using harmonised pharmacopoeial procedures where feasible; if only Class 3 solvents are present, a properly validated non-specific method such as loss on drying may be used. Class 1 solvents likely to be present should be identified and quantified, and Class 2 or Class 3 solvents above their Option 1 limits or 0.5% should be identified and quantified. [1]
Q3C also says testing is only necessary for solvents used or produced in manufacture or purification. [1] That is why the first question to a supplier is which solvents the process uses. A certificate that reports one solvent tells you nothing about the others.
Elemental impurities in ICH Q3D(R2)
Q3D classifies arsenic, cadmium, mercury and lead as Class 1 elements: human toxicants with limited or no use in pharmaceutical manufacture, typically entering from materials such as mined excipients, which require evaluation during risk assessment. Testing is applied when the risk assessment identifies it as the appropriate control. Q3D's scope includes drug products containing synthetically produced polypeptides. [2]
A research-grade "heavy metals" line may use an older or different method. Record the method name, the elements reported and the units exactly; do not convert a generic "heavy metals" result into element-specific values.
A fictional certificate line
An invented certificate states "Residual solvents: conforms." There is no solvent name, method or value. The note reads: "Residual solvent line present without solvent identity, method or result; process solvents not stated; requested solvent list and results." That is more useful than either accepting the word "conforms" or treating the line as a failure.
Nothing on this page sets a safe level for any use. The ppm figures quoted are ICH examples for pharmaceutical products, recorded here so you can read a certificate that cites them.
Check the underlying evidence
Sources & review dates
- ICH Q3C(R9): Impurities, Guideline for Residual Solvents (Step 4, 24 January 2024) ↗Accessed 13 Oct 2026
- ICH Q3D(R2): Guideline for Elemental Impurities (adopted 26 April 2022) ↗Accessed 13 Oct 2026
Sources are documentary evidence. They do not establish firsthand testing of a listed supplier.