Analysis of Residual Solvents According to the New ICH Q3C Guideline

The ICH Guideline for Residual Solvents in Pharmaceuticals ICH Q3C(R8) Step 4 Version was issued in April 2021, and specifies a new PDE (Permitted Daily Exposure) for the following three components: 2-Methyltetrahydrofuran (2-MTHF), Cyclopentyl Methyl Ether (CPME), and Tertiary Butyl Alcohol (TBA). As a result, CPME and TBA will be placed into Class 2 solvents and 2-MTHF will be placed into Class 3 solvents. The headspace GC method is mainly used for analysis of residual solvents in pharmaceuticals. Class 1 and Class 2 solvents, which pose a high risk to human health, are particularly strictly controlled. Here we present an example residual solvent analysis of Class 2 solvents, including CPME and TBA, in pharmaceuticals.