Pharmaceutical NEWS - Fall 2008

Residual Solvents: A volatile subject

After much discussion and many revisions, the USP General Chapter <467> on Residual Solvents became effective on July 1, 2008, replacing the previous version, known as Organic Volatile Impurities. Many drug products and substances are included in the broad scope of this chapter, which is aimed at identifying unsafe levels of solvents remaining in finished products.

Analysts face multiple challenges when performing the tests as listed in the USP, including identifying what solvents may be present in the products, determining solubility of the products in a suitable solvent and matrix interference with the chromatographic methods. To assist clients in understanding the test options, Lancaster Laboratories has developed a fact sheet on Residual Solvents

Having complete information about the product to be tested is key to ensuring efficient residual solvents testing. So the fact sheet includes a list of information analysts will need to perform the test, such as a list of solvents used to manufacture the product and whether the product is water-soluble or water-insoluble.

The USP methods describe procedures A, B and C, which use headspace gas chromatography for qualitative and quantitative determinations of residual solvents. Initial testing is performed to determine if there are any peaks representing solvents that are above the allowable limits, and any presumptive positive results are further confirmed and quantitated. Lancaster Labs has extensive experience in performing residual solvent testing by USP <467>. “We’ve tested more than 35 materials using the new methods,” says Terry Schuck, a group leader in the Raw Materials Department.

In addition to running the published methods, Schuck and the analysts who work with him have also developed methods for analyzing solvents that do not fit into the USP testing scheme. “Some of the class 2 compounds and all of the class 3 compounds can’t be analyzed using the headspace technique listed in the General Chapter, so an alternative method may need to be developed for that material,” he explains. To determine residual solvents that fall outside the USP methods, Lancaster Labs analysts sometimes use a technique referred to as a self-validating method. This involves analyzing a sample fortified with the solvents at various concentrations and using the recovery data to determine if the residual solvent is above the limit.

Because the USP methods are complex and not appropriate for all materials, many manufacturers have turned to Lancaster Labs for expertise in developing methods and analyzing their products to ensure compliance with the new requirements. For more information on residual solvent testing, contact Pharmaceutical Business Development at 717-656-2300.