Application of Gas Chromatography (GC) in a GMP Pharmaceutical Laboratory

Gas chromatography (GC) is one of the fundamental analytical techniques used in pharmaceutical laboratories. It is widely applied in the analysis of volatile and semi-volatile compounds, in particular residual solvents, process-related impurities, and some active pharmaceutical ingredients (APIs) and their derivatives.

In routine laboratory practice, two main approaches are used for introducing samples into a gas chromatograph.

Headspace GC (HS-GC) The headspace technique is based on the analysis of the gas phase above the sample. This method is particularly valued because it:

• minimizes contact between the sample matrix and the chromatographic system,
• reduces the risk of contamination of the column and injector,
• ensures high repeatability and stability of results.

HS-GC is the reference method for the determination of residual solvents in accordance with pharmacopoeial requirements and ICH guidelines.

Direct Injection GC In direct injection, the sample is introduced directly into the GC injector. This approach requires increased control of sample cleanliness and appropriate validation with respect to matrix effects.

FID and NPD Detection Various types of detectors are commonly used in gas chromatography, in MT Laboratories the following detectors are available:

• FID (Flame Ionization Detector) – a universal, highly stable, and sensitive detector for organic compounds, especially hydrocarbons; ideal for routine quality control,
• NPD (Nitrogen-Phosphorus Detector) – a selective detector used for the determination of compounds containing nitrogen and phosphorus, such as amines, nitrogen-containing compounds, or selected APIs.

Carrier Gas in GC MT Laboratories uses the following carrier gases:

• helium – providing excellent separation performance and stability,
• nitrogen – a cost-effective alternative, increasingly used in GMP laboratories, particularly in combination with FID and NPD detection.

The choice of carrier gas should be justified and documented within the method validation documentation.

In summary, gas chromatography using headspace and direct injection techniques, combined with FID and NPD detection, is an indispensable tool in pharmaceutical quality control. Properly validated GC methods support compliance with GMP requirements, ensure data integrity, and deliver high-quality and reliable analytical results.