19th September 2016
Method implications on lab gas supply for Residual Solvent Analysis using HS-GC-FID
Method implications on lab gas supply for Residual Solvent Analysis using HS-GC-FID - as featured in The European Pharmaceutical Manufacturer Magazine.
In the manufacturing or processing of drugs and pharmaceuticals, any solvents used in production must be absent from the end-product since they are potentially harmful to those consuming pharmaceutical products. Residual solvent analysis (RSA) allows identification of by-products of manufacturing with concentrations tested, analysed and monitored to ensure levels present are below the limits set by the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH). The United States Pharmacopeia (USP) and ASTM have developed methods for identifying residual solvents with the use of a headspace (HS) extraction alongside a Gas Chromatograph (GC) with a Flame Ionisation Detector (FID).
Residual solvents are classified according to their toxicity as follows:
Class 1 solvents: Solvents to be avoided. Known human carcinogens, strongly suspected human carcinogens and environmental hazards.
Class 2 solvents: Solvents to be limited. Non-genotoxic animal carcinogens or possible causative agents of other irreversible toxicity such as neurotoxicity or teratogenicity. Solvents suspected of other significant but reversible toxicities.
Class 3 solvents: Solvents with low toxic potential. Solvents with low toxic potential to man; no health-based exposure limit is needed. Class 3 solvents have Permitted Daily Exposure (PDE) of 50 mg or more per day.
RSA is the most common use for GCs in the Pharmaceutical industry and the world’s leading instrument manufacturers have created custom solutions with headspace and GC, FID and MS combinations tailored to meet a lab’s particular demands. These instruments require highly pure gases, meaning that laboratory managers have the choice between traditional gas supply methods or gas generator supply.
The method for RSA, in accordance with the USP, requires the use of either nitrogen or helium as carrier gas and the FID will require hydrogen flame gas along with air or Zero Air flame support gas. Nitrogen is widely used as a carrier gas for RSA, and is used for the HS-GC-FID of Spironolactone and can be generated in the laboratory using a gas generator. Recently, there has been increased focus on use of nitrogen as an alternative carrier gas to helium, with small changes to methods along with shorter columns allowing identical analysis times.
The ASTM method, F 1884-04, for residual solvent analysis in pharmaceutical packaging material, does not define a carrier gas. This means that labs can choose the most optimum and efficient gas for their analysis. There are clear advantages to be found from opting for hydrogen carrier gas for GC in this circumstance, with faster run times allowing higher sample throughput as well as the aforementioned benefits of removing gas cylinders from the lab.
Analysis methods in the Pharmaceutical industry are highly regulated, meaning that labs are unable to freely choose which gases they use in particular methods. For labs looking to simplify their overall workflow, a gas generator can help significantly. Generating gas in the lab can improve productivity through providing a round-the-clock gas supply, without the need to changeover cylinders, wait for gas deliveries or having to manage stock levels. The removing of cylinders from the lab has clear benefits for lab efficiency and the use of nitrogen carrier gas does not necessarily mean slower analysis compared with helium.
- United States Pharmacopeia
- ASTM method, F 1884-04
- International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use