Residual Solvents

Changes to USP chapter residual solvents have affected manufacturers of pharmaceutical products and contract testing laboratories.

Butterworth applies headspace analysis to residual solvents and raised concerns with the USP regarding the new procedure including:

• An aqueous dilution of hydrophobic solvents used in the preparation of standard stock solutions, which lead to inaccuracies due to solvent loss
• Not all water-insoluble materials such as magnesium stearate are soluble in prescribed dimethylformamide (DMF) and dimethyl sulfoxide (DMSO) solvents
• Not all manufacturers G43 phase columns stipulated in the procedure meet the resolution system suitability requirement

Butterworth agreed on enhancements made to the procedure, which are not considered to be deviations and demonstrated a significant improvement in the performance of the procedure.

This included modification and simplification of aqueous dilution steps to prevent solvent loss, which improves accuracy, signal to noise ratios, peak integrations and system suitability.

Similar enhancements to the sample preparation scheme for water-insoluble articles resulted in comparable improvements, especially accuracy, with the added environmental benefit of reducing the amount of DMF and DMSO consumed.

In addition, fewer dilution steps saved a significant amount of time for the analyst.

The USP states that a Phase G43 column is a preferred phase. We identified a column manufacturer whose product provides a greater selectivity and reproducibility than most in the market, increasing confidence in peak allocation and integration.