Headspace-gas Chromatography
Analysis of Residual Solvents in
Pharmaceuticals
The latent toxicity of organic residual solvents in pharmaceuticals has gradually become
recognized. At present, the Pharmacopoeia of each country contains the residual solvent
inspection method. The International Conference on Harmonization (ICH) is divided into
three categories according to the degree of harm to the human body and environment for
the 69 organic solvents commonly used in the production and purification of
pharmaceuticals. For pharmaceutical companies, the analysis of residual solvents is an
essential part of the production process. Among them, the most commonly used
detection method is headspace gas chromatography.
Introduction
Headspace gas chromatography is also known as liquid-gas chromatography. It has the
characteristics of faster analysis speed, no need to extract with an organic solvent, easy
operation, and little harm to analysts and environment. The principle is that the sample to
be tested is placed in a closed container, and the volatile components are volatilized from
the sample matrix by heating (Figure 1). Equilibrium is achieved in the gas-liquid (or gas-
solid) phase, and the top gas is directly extracted for chromatographic analysis to
examine the composition and content of volatile components in the sample. The use of
headspace sampling technology eliminates the tedious and tedious sample preparation
process, avoids the interference of organic solvents on the analysis, and reduces
contamination of the column and inlet.
Fig. 1. Schematic diagram of a pressure balances static headspace system1.
Application of Headspace-gas Chromatography
in the Detection of Residual Solvents
Limits for five organic volatile impurities (benzene, chloroform, dioxane, methylene
chloride, and trinitroethylene) are specified in USP41-NF36, which is determined by static
head-space analysis. Since the head-space sampler is extremely easy to achieve
solvent-free extraction of liquid and solid sample