Foothill Ranch, CA
Static headspace gas chromatography with flame ionization detection at a cGMP, FDA-registered, DEA-licensed laboratory. Class 1, 2, and 3 solvents to USP <467> and ICH Q3C on drug substances, drug products, and excipients. GC-MS capabilities to confirm identification of compound if desired. Send a specific material and a chemist scopes it directly.
Residual solvents are volatile organic chemicals used or produced in the manufacture of a drug substance, excipient, or drug product, and not fully removed by processing. USP General Chapter <467> is the compendial method for controlling them, harmonized with ICH Q3C, which classifies solvents by toxicity and sets limits.
The technique is static headspace gas chromatography. The sample is sealed in a heated vial so the volatile solvents partition into the gas above it, and only that headspace is injected, which keeps the non volatile matrix out of the instrument. Flame ionization detection quantifies the separated solvents. ACTA uses GC-MS to support identification if desired by the client.
ACTA follows USP, BP, JP, and EP methods, or develops and validates a method when a solvent is not addressed by the compendial procedure. One nuance worth knowing: ICH Q3C applies to new drug products, while USP <467> applies the same limits to new and existing products.
ICH Q3C sorts solvents into three classes. The permitted daily exposure, or PDE, is the amount of a solvent a patient can receive per day, and it converts to a concentration limit in the product based on the daily dose.
Solvents with unacceptable toxicity, such as benzene and carbon tetrachloride. Known or suspected human carcinogens and environmental hazards, controlled to the lowest levels.
Solvents to be limited, such as methanol, acetonitrile, and methylene chloride, each controlled to a permitted daily exposure and a concentration limit.
Solvents with low toxic potential, such as ethanol and acetone, generally acceptable up to 50 mg per day without further justification.
USP <467> runs as a screen, a confirmation, and a quantitation. A material that passes the screen is done. Only a solvent that appears over its limit moves forward.
Headspace GC-FID on a USP G43 column screens Class 1 and Class 2 solvents against their limits. A material that meets every limit here is reported and complete.
Any solvent that appears to exceed its limit in Procedure A is confirmed on a USP G16 column, an orthogonal separation that rules out a coeluting interference.
A quantitative determination for any solvent that does not meet its limit under Procedures A and B, reporting a result in ppm per solvent with chromatograms.
For a Class 1 solvent at trace level, or any solvent whose identity is in question, ACTA can confirm the identification by GC-MS. The mass spectrum is a structural fingerprint matched against reference libraries, stronger evidence of identity than retention time alone. For quantitation by gas chromatography generally, see GC analysis and testing.
Most work is a compendial screen against the USP <467> and ICH Q3C class limits, with a pass or limit report as the deliverable. When a result is over a limit, Procedure C returns a quantified ppm value per solvent.
When a process uses a solvent that is not addressed by the compendial procedure, ACTA develops and validates a product specific method to ICH Q2, so the solvent you actually use is the one that gets measured.
As the big labs consolidate, they have stopped taking projects that are not large enough, and just getting into their queue can take a month. ACTA is FDA-registered, DEA-licensed, and cGMP, and small enough to actually respond and follow up. Many of our largest accounts started as one residual solvents test.
Compound identification and quantitation by GC-MS for solvents and unknown volatiles.
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Product specific methods for solvents outside the compendial procedure, to USP and ICH.
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USP <232> and <233> elemental impurities by ICP-MS.
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Compendial and custom methods across instruments.
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