The aim of this study was to develop a rapid, cost-effective, modified USP <467> HS-GC-FID method for residual solvent determination in pharmaceutical products using the Thermo Scientific™ TriPlus™ 500 Headspace Autosampler and nitrogen as carrier gas.
Introduction
Organic solvents are often used in the manufacturing and purification of drug substances but due to their potential toxicity their absence/presence must be verified in the pharmaceutical products to ensure patient safety. The United States Pharmacopeia (USP) method <467>provides detailed procedures for screening, confirmation and quantitation of residual solvents, including sample preparation and analytical conditions.
Gas chromatography (GC) coupled with headspace (HS) sampling technique and flame ionization detection (FID) as detector is the analytical method specified in USP <467> for this application, as most of the target compounds are organic solvents with relatively low boiling points and good thermal stability.
In this technical note, the USP <467> method for Class 2A solvent was modified as an example of how the
residual solvent analysis can be improved with a faster and cost-effective alternative method.
Conclusions
Using the experimental conditions described the modified USP <467> method is a real alternative to
classical conditions for residual solvent analysis offering the advantages of:
- a rapid (×7 improvement in analysis speed); cost effective (with nitrogen as carrier gas)
- high throughput analysis (up to 240 samples analyzed uninterrupted in a single sequence).
Results show that method optimization with nitrogen as carrier gas and TG-624 SilMS capillary column
together with Chromeleon CDS represents a viable alternative for routine laboratories.