Residual solvents are organic volatile impurities in drug substances and drug products that are byproducts of manufacturing.  Drug manufacturers need to ensure that these residual solvents are at or below acceptable levels.

The USP <467> sets the concentration limit for each solvent. Solvents are grouped according to their toxicity levels and potential adverse effects.    Class 1 solvents are known to cause unacceptable toxicities or to have environmental effects and should be avoided in the manufacturing process. Class 2 solvents are nongenotoxic animal carcinogens, and concentrations of these compounds should be limited.  Class 3 solvents are less toxic and should be used when practical.

Gas Chromatography with valve-and-loop headspace analysis is used for identification and quantification of residual solvents in drug substances and drug products.

Following USP <467>, three analytical procedures are used for identification and quantification of the residual solvents:

• Procedure A screens for and confirms the solvents’ presence.
• Procedure B confirms the solvents’ identity.
• Procedure C is required to quantify the amount of residual solvents present.

At Pine Lake Laboratories, we have extensive experience in the determination of residual solvents in a wide variety of drug substances, excipients or drug products.

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