Residual solvents in pharmaceutical products are organic volatile compounds that are used or created when drug substances, excipients, or additives are manufactured, prepared, or packaged and stored. Residual solvents are often crucial in the synthesis of drug substances because they are necessary to ameliorate the quality of drug substances or excipients. However, because they have no therapeutic value, if residual solvents are not completely removed by practical manufacturing methodologies, they must be evaluated and justified. Pharmaceutical products should contain low levels of residual solvents as determined by safety data. However, residual solvents may be harmful to human health and to the environment if their presence exceeds tolerance limits as determined by safety data. As a result, residual solvents testing has become an important quality control player in pharmaceuticals.
In recent years, testing for residual solvents has grown as the demand by the FDA for such testing has increased. New Jersey Laboratories owns the latest technology in this space, called Headspace GC (GC-HS). GC-HS is ideal because of its ability to quantify individual solvents. The term “headspace” refers to that portion of the sample container above the sample material where gas or vapor accumulates. Headspace analysis focuses upon analyzing this gas or vapor phase, which typically contains volatile organic compounds (VOCs), residual solvents or other substances that can be released from the sample into the headspace. The headspace technique also allows for the analysis of volatile compounds present in the sample without necessarily introducing the entire sample into the instrument. This is particularly useful for samples that are sensitive to temperature changes or where direct introduction of the sample may alter its composition or characteristics. Some examples of volatile compounds that fit this description include the following:
Headspace analysis allows for the controlled extraction and analysis of these volatile compounds without exposing them to the direct analytical system, mitigating potential alterations in composition or characteristics that might occur with direct sample introduction. Although most laboratories do basic testing on residual solvents, New Jersey Laboratories also performs more difficult tests on solvents such as poloxamers which are excipients that can also aid in drug delivery. We are highly proficient in residual solvent analysis by headspace gas chromatography and can walk you through every step.
We perform the following methods for residual solvents:
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| USP Chapter | Test |
| <467> | Organic Volatile Impurities |
The International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals (ICH) categorizes residual solvents into three classes based on toxicity and potential risks to human health. These classifications have been widely adopted by regulatory agencies and pharmacopeias throughout the world including the United States Pharmacopeia (USP). Class 1 solvents are known to carcinogenic or highly toxic and are to be avoided. Class 2 solvents have low toxic potential but may cause adverse effects if they exceed the acceptable daily intake (ADI) and the maximum daily dose of the pharmaceutical product. Finally, Class 3 solvents have low toxic potential and are generally regarded as safe for pharmaceutical use at low levels. Implementing methods such as USP <467> (above) requires specialized equipment with careful selection of operating parameters. Our scientists have extensive experience in meeting your gas chromatography and residual solvent testing requirements.
