Residual solvents testing is used in the pharmaceutical industry in order to detect and quantify organic volatile chemicals that are used (or produced) in the manufacturing of drug substances, excipients, and drug products. Samples are evaluated, at a residual solvents testing lab like Nucro-Technics, to ensure that traces of these volatile chemicals are below permitted daily exposure limits.  This helps to avoid contamination and product failures, while ensuring that product is safe for human use. The most common approach is to follow the USP <467> Residual Solvents monograph.

How Residual Solvents Testing is Performed

Most commonly, residual solvents testing is conducted in raw materials that are being used for manufacture, as this is the safest approach. If following the USP monograph, there are three procedures that could be followed depending on what is trying to be achieved: Procedure A, Procedure B, and Procedure C. All procedures would require the use of a Gas Chromatograph (GC).

Procedure A is an identification and limit test that is used for general screening to confirm the absence or presence of residual solvents. If a raw material or drug substance from a new manufacturer needs to be evaluated, or if certain solvents likely to be present, this is typically where the residual solvents lab testing process begins.

Procedure B is a confirmatory identification and limit test for Procedure A. A different column is used, and this test can typically overcome any matrix effects that may have been present in the Procedure A testing. If peak areas in the sample are greater than in the standard solution, further evaluation is needed.

Procedure C is a quantitative test where specific solvents (such as Ethanol and Acetone) are evaluated. This is done by conducting a spike recovery in the samples where one would spike the relevant solvent at the limit level and back-calculate to determine the quantity of excess solvent that would be present in a particular sample.

For each test matrix, method verification (typically of Procedure C) is needed to demonstrate the reliability of the compendial method from USP <467> at a residual solvents testing lab like Nucro-Technics. This type of analytical activity is performed on a daily basis at our facility and the organization can offer a turnkey approach to meeting these specific GMP regulatory testing requirements.