Lab Testing & Quality
Residual Solvent Testing
At-a-glance comparison
| Spec | Value |
|---|---|
| Standards reference | ICH Q3C(R8) Guideline for Residual Solvents (2021 or current) |
| Solvent classifications | Class 1: avoid (e.g., benzene, carbon tetrachloride); Class 2: limit (e.g., methanol, hexane, dichloromethane); Class 3: low toxicity (e.g., ethanol, acetone, ethyl acetate) |
| Standard analytical method | Gas chromatography with flame-ionization (GC-FID) or mass-spectrometry (GC-MS) detection |
| When it applies | Whenever extraction or manufacturing processes use organic solvents, including for extracted, concentrated, and isolated 7-OH products |
| Where results appear | On every reputable extracted-product Certificate of Analysis |
What is residual solvent testing?
When a product is manufactured using organic solvents - for example, ethanol or hexane used to extract alkaloids from plant material - small quantities of those solvents can remain in the finished product. Residual solvent testing measures the concentration of these trace solvents to confirm that they are below toxicologically acceptable limits.
For kratom alkaloid products, residual solvent testing is most relevant to extracts, concentrates, and isolated 7-hydroxymitragynine products manufactured using solvent-based processes. Whole-leaf or simple powdered products that are not solvent-extracted typically do not require residual solvent testing.
ICH Q3C classification framework
The International Council for Harmonisation guideline ICH Q3C provides the international framework for residual solvent classification and acceptance criteria. The guideline classifies organic solvents into three classes by toxicity. Class 1 solvents - including benzene, carbon tetrachloride, 1,1-dichloroethene, 1,1,1-trichloroethane, and 1,2-dichloroethane - are to be avoided in manufacturing because of their known or suspected toxicity. Class 2 solvents - including methanol, dichloromethane, hexane, acetonitrile, and many others - are to be limited; ICH Q3C specifies a permitted daily exposure (PDE) for each. Class 3 solvents - including ethanol, acetone, ethyl acetate, isopropanol, and others - have low toxicity in animal studies and have a default daily exposure limit of 50 mg/day in the absence of more specific information.
Compliance is determined by comparing the measured concentration of each detected solvent in the product against the corresponding ICH Q3C limit, taking labeled serving size into account.
How residual solvents are measured
The standard analytical method is gas chromatography (GC), typically with either flame-ionization detection (GC-FID) for routine quantification or mass-spectrometry detection (GC-MS) for confirmatory identification. Sample preparation often uses headspace gas chromatography, in which the sample is heated in a sealed vial and a portion of the headspace gas is sampled, allowing volatile solvents to be measured without injecting the sample matrix into the chromatographic column.
Validated methods are described in United States Pharmacopeia chapter , which incorporates the ICH Q3C limits and provides specific chromatographic procedures. The Certificate of Analysis should disclose which method was used and the result and limit for each solvent tested.
Common questions about residual solvent testing
- What are residual solvents?
- Residual solvents are trace amounts of organic solvents that may remain in a product after extraction or other manufacturing operations. Residual solvent testing confirms they are below toxicologically acceptable limits.
- What is ICH Q3C?
- ICH Q3C is the International Council for Harmonisation guideline that classifies organic solvents by toxicity (Class 1, 2, or 3) and specifies acceptable daily exposure limits. It is the international standard for residual solvent control.
- Do all kratom products require residual solvent testing?
- Residual solvent testing is most relevant to extracted, concentrated, and isolated 7-OH products manufactured using solvent-based processes. Whole-leaf or simple powdered products that are not solvent-extracted typically do not require this test.
- What method is used for residual solvent testing?
- Gas chromatography (GC), typically with flame-ionization detection (GC-FID) for quantification or mass-spectrometry detection (GC-MS) for confirmation. Headspace sampling is common for volatile-solvent analysis.
- What does 'pass' mean for residual solvent testing?
- It means the measured concentration of each detected solvent is below the applicable ICH Q3C acceptance limit, after taking labeled serving size into account.
- What are some Class 1, 2, and 3 solvents?
- Class 1 (avoid): benzene, carbon tetrachloride, 1,2-dichloroethane. Class 2 (limit): methanol, hexane, dichloromethane, acetonitrile. Class 3 (low toxicity): ethanol, acetone, ethyl acetate, isopropanol. The full classified list is in ICH Q3C.
Related glossary terms
References
- International Council for Harmonisation. (2021). ICH Q3C(R8) Guideline for Residual Solvents.
- United States Pharmacopeia. (2024). General Chapter Residual Solvents.
- American Kratom Association. AKA GMP Standards Program. https://www.americankratom.org/aka-gmp-program
Important safety information:
Products containing 7-hydroxymitragynine (7-OH) are sold for adult use only (21+). These statements have not been evaluated by the U.S. Food and Drug Administration. Products are not intended to diagnose, treat, cure, or prevent any disease. The FDA has raised safety concerns regarding concentrated 7-OH products; consult a qualified healthcare professional before use. Do not operate vehicles or machinery after use. Keep out of reach of children and pets. Laws vary by state, buyers are responsible for knowing applicable law.