Residual Solvent Testing for Extracts | Verified Analytical Laboratory

What are residual solvents?

Residual solvents are organic chemicals used to make, extract or purify an ingredient that the process does not completely remove. ICH Q3C states the principle directly: "Since there is no therapeutic benefit from residual solvents, all residual solvents should be removed to the extent possible to meet product specifications, good manufacturing practices, or other quality-based requirements." Testing shows how much is actually left in the finished material.

ICH Q3C sorts solvents into three classes by toxicity. It expresses limits in two ways: a permitted daily exposure (PDE), the amount in milligrams per day considered acceptable, and a concentration limit in parts per million (ppm).

What are the ICH Q3C solvent classes and limits?

Class 1, solvents to be avoided: "Known human carcinogens, strongly suspected human carcinogens, and environmental hazards."
Class 2, solvents to be limited: "Non-genotoxic animal carcinogens or possible causative agents of other irreversible toxicity such as neurotoxicity or teratogenicity", and "Solvents suspected of other significant but reversible toxicities."
Class 3, solvents with low toxic potential: "no health-based exposure limit is needed. Class 3 solvents have PDEs of 50 mg or more per day."

Selected limits from ICH Q3C(R9), Impurities: Guideline for Residual Solvents, Tables 1 to 3 (Step 4 version dated 24 January 2024).

Class	Solvent	PDE (mg/day)	Concentration limit (ppm)
1	Benzene	Not given	2
1	Carbon tetrachloride	Not given	4
1	1,2-Dichloroethane	Not given	5
1	1,1-Dichloroethene	Not given	8
1	1,1,1-Trichloroethane	Not given	1500
2	Acetonitrile	4.1	410
2	Chloroform	0.6	60
2	Cyclohexane	38.8	3880
2	Dichloromethane	6.0	600
2	Hexane	2.9	290
2	Methanol	30.0	3000
2	Tetrahydrofuran	7.2	720
2	Toluene	8.9	890
2	Xylene (usually 60% m-xylene, 14% p-xylene, 9% o-xylene with 17% ethyl benzene)	21.7	2170
3	Acetone, ethanol, ethyl acetate, heptane, pentane, 2-propanol and others in Table 3	50 mg per day or less acceptable without justification	5000 ppm or 0.5% under Option 1

Figures checked against the sources below on 3 November 2026; rules change, so confirm the current version before relying on them.

ICH has a Q3C(R10) revision under way: its 2026 work plan covers revised monographs for dimethylformamide, dichloromethane and ethylene glycol and a revised core table, with Step 4 adoption targeted for March 2027. Recheck Table 2 values once it is final.

How do ppm limits relate to daily intake?

The Class 2 ppm values are ICH's "Option 1" limits. They were calculated with the equation concentration (ppm) = 1000 × PDE ÷ dose, where PDE is in mg/day and dose is in g/day, "by assuming a product mass of 10 g administered daily." Products taken at more than 10 g per day "should be considered under Option 2", which applies the same equation to the product's real maximum daily dose. Option 2 limits are acceptable "provided that it has been demonstrated that the residual solvent has been reduced to the practical minimum."

Worked example with illustrative doses: hexane has a PDE of 2.9 mg/day.

A softgel product with a maximum daily intake of 2 g: 1000 × 2.9 ÷ 2 = 1450 ppm under Option 2, compared with 290 ppm under Option 1.
A protein-style powder taken at 20 g per day: 1000 × 2.9 ÷ 20 = 145 ppm, which is tighter than the Option 1 table value.

Large servings are where solvent residues matter most. Compare your result with the limit calculated for your product's real daily intake, not only with the table value.

What is USP 467 and does it apply to supplements?

USP General Chapter <467> Residual Solvents is the United States Pharmacopeia chapter on solvent control. FDA's guidance on residual solvents records that "On July 1, 2008, the USP implemented a requirement for the control of residual solvents in drug products marketed in the United States," replacing the older chapter <467> "Organic Volatile Impurities." The chapter includes its own analytical procedures, and for drug products FDA "will accept the use of appropriate analytical procedures other than those included in General Chapter <467>" when they are properly validated. The same guidance points to ICH Q3C for solvent classification and permitted daily exposures.

No federal rule names USP <467> or ICH Q3C as the limit for dietary supplements. The supplement CGMP rule instead requires manufacturers to set limits on contamination that may adulterate a product, under 21 CFR 111.70(b)(3), and many extract and ingredient specifications use the ICH Q3C numbers to do it. The official text of <467> is published in the USP-NF, so check the current chapter if your buyer's specification cites it.

Why are hemp and botanical extracts tested?

Extraction leaves traces. Ethanol, hexane, heptane, acetone and hydrocarbon gases such as butane and propane are used to pull compounds out of plant material, and purging or evaporation does not always remove all of the solvent.
Serving size changes the math. An extract taken in small amounts may meet a calculated limit easily, while the same extract blended into a large daily serving faces a tighter one.
Some solvents have no ICH value. Butane and propane are not classified in Q3C, and petroleum ether is listed in Table 4, "Solvents for which no adequate toxicological data was found", for which manufacturers "should supply justification for residual levels". For these, state hemp rules or the buyer's specification set the number.
Buyers and states ask for it. Many state hemp programs include residual solvents in their product testing rules, and extract buyers often list a solvent panel on their specification sheets.

How are residual solvent results reported?

Results are reported for each solvent in ppm, which is the same as micrograms per gram (µg/g) of sample. Headspace gas chromatography (HS-GC), the technique listed for this panel on our contaminant testing page, is the standard way to measure volatile solvents: it analyzes the vapor above a heated, sealed sample rather than the sample itself. A useful report shows:

each solvent tested, with a result or a below-LOQ entry;
the LOQ for each solvent, which should sit well below the limit you need to meet;
the limit applied, and whether it is an ICH Option 1 value, a dose-adjusted Option 2 value, a state limit or a buyer limit;
whether each result meets that limit.

ICH Q3C notes that "It is only necessary to test for solvents that are used or produced in the manufacture or purification" of a product, so list every solvent used in your process when you request a quote. We use that list to recommend a panel, and we confirm the method and sample amount with your quote.

Questions about this page

Does CO2 extraction leave residual solvents?

Supercritical carbon dioxide turns back into a gas when the pressure is released, so it does not leave a residue the way hexane or ethanol can. Many CO2 extracts are still winterized or diluted with ethanol or another solvent afterward, so ask your supplier which solvents touched the material at any step and test for those.

What is the difference between a PDE and a ppm limit?

A PDE (permitted daily exposure) is the amount of a solvent, in milligrams per day, that ICH Q3C considers acceptable to take in. A ppm limit converts that amount into a concentration for a given daily intake. ICH's Table 2 ppm values assume 10 g of product per day, so products taken in larger amounts need a lower ppm limit.

Can Class 3 solvents be ignored?

No. Class 3 solvents have low toxic potential, and ICH Q3C treats 50 mg per day or less as acceptable without justification, but they still count toward the result. ICH allows a non-specific test such as loss on drying, if properly validated, when only Class 3 solvents are present; results by individual solvent are more useful when a buyer asks for them.

Do I need to retest after changing my extraction process?

A process change is the usual trigger for new data. A new solvent, a different solvent grade, a changed drying or purging step or a new extraction contractor can all change what remains in the finished material. Testing the first lots made after the change shows whether the residue profile still meets your specification.

Why does my CoA show a solvent I never used?

Solvents can come from upstream: a supplier's extraction step, an ingredient processed with a solvent, or a carrier or excipient. ICH Q3C allows solvent levels in a product to be assessed from the levels in each component, which is why supplier documentation for every ingredient matters when an unexpected solvent appears on a report.

Sources: ICH Q3C(R9) Impurities: Guideline for Residual Solvents (Step 4, 24 January 2024) · ICH Q3C(R10) Expert Working Group work plan (2026) · FDA Guidance for Industry: Residual Solvents in Drug Products Marketed in the United States (November 2009) · 21 CFR 111.70: What specifications must you establish? (eCFR)
Last reviewed: 3 November 2026

Residual solvent testing for extracts and supplements