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Residual Solvents

Residual Solvents by USP <467>

USP <467> contains limits for residual solvents in pharmaceutical substances along with procedures for measuring residual solvent concentrations.  Residual solvent limits are based on their toxicity and hazards.  Solvents are ranked into one of three classes: compounds in Class 1 are considered the most toxic/hazardous.  Compounds in Class 3 are considered the least toxic/hazardous.  The general chapter also contains three procedures for measuring residual solvent concentrations.  A list of the solvents in the scope of USP <467> is presented in the Appendix of the general chapter.

Method

The methodology is given in USP <467>.  Three (3) procedures each are given for water soluble and water insoluble articles.  One of the three procedures must be used according to decision criteria given in the general chapter. USP <467> relies on Gas Chromatography - Flame Ionization Detection (GC-FID) for analysis.  Click here to see more information on GC-FID.

Procedures

Each of the procedures in USP <467> can be characterized as follows:
  • Procedure 1: Analysis of the test solution and comparison to an external standard
  • Procedure 2: Analysis of the test solution on a secondary column and comparison to an external standard
  • Procedure 3: Quantification of the analyte solvent