Headspace Gas Chromatography (GC-HS): How To control OVIs

Introduction and Outcome: GC-HS

GC-HS plays an important role in pharmaceutical development as it enhances quality by controlling OVI. In this article, I will discuss the GC-HS principles, its process, method development approach, applications, advantages and calculations with case studies and FAQs.

GC-HS

GC-HS is the combination of GC (gas chromatograph) and HS (head Space). It is highly sensitive instrument and can detect even trace amounts of volatile compounds.

GC-HS = GC + HS

GC

It is a powerful analytical technique used to separate and analyze organic volatile compounds

Check out this article for more details about the GC: GC Method Development

Headspace (HS)

In GC-HS analysis, a sample is sealed in a vial, and the volatile compounds in the headspace (the gas phase above the sample) are allowed to equilibrate. These volatile compounds are then injected into the GC system for analysis.This method is especially useful for analyzing the volatile components in solid or liquid samples, such as solvents, residual solvents, or perfumes in pharmaceuticals.

Conditions for GC-HS analysis

GC-HS requires that the OVIs of interest have high volatility, while the rest of the sample/pharmaceutical is much less or non-volatile. GC-HS is used for analysis of the following type of residual solvents in the pharmaceuticals/samples:

Class 1 solvents such as Benzene, Carbon Tetrachloride, 1,2-dichloroethane, 1,1-dichloroethane and 1,1,1-trichloroethane
Class 2 solvents such as acetonitrile, acetone, methanol, toluene etc.
Class 3 solvents such as acetic acid, isopropyl alcohol etc.
Any other volatile solvents

Headspace Gas Chromatography (GC-HS) — Image created in CANVA

HS GC-MS

When the mass detector is used with GC-HS then it is called HC GC-MS. It is used for the identification and structure elucidation of unknown organic volatile impurities

9 Steps GC-HS Procedure

The standard of residual solvents are prepared as per their specification/limit
The specified volume of the standard is added in the GC-HS vail and the vial is sealed immediately to avoid any evaluation
A known amount of sample is placed in the GC-HS vial
Diluent is added as per the method in the GC-HS sample vial and then the vial is sealed immediately (to avoid any evaluation).
The vial is heated to a specific temperature, allowing volatile compounds to evaporate into the headspace.
The vapor from the headspace is sampled and injected into the GC system.
The organic volatile solvents/impurities are separated in the GC capillary column and then go into the detector. The detector detects the eluted solvent and concert into the peak
Then the concentration of each OVI is calculated based on the area response of the concerned OVI in the standard and in the sample
Then result is reported

GC-HS Method Development Steps

Selection of Diluent
Standard preparation
Sample preparation

How to Select Headspace Gas Chromatography (GC-HS) Diluent?

In GC-HS analysis, the selection of a diluent is crucial for ensuring accurate results and preventing problems like overloading the detector or interfering with the analysis due to carry-over. The following points to be considered while selecting the GC-HS diluent:

Purity
Volatility
Chemical Inertness
Solubility of Sample Components and
Water Content

Purity

Ensure that the diluent used is of high purity, free from contaminants that might affect the analyte quantification or interfere with the detector response.Only Gc-HS grade solvents should be used for sample and standard preparation

Volatility

The diluent should have a boiling point higher than the analytes of interest but not so high that it won’t volatilize in the headspace analysis. The diluent must be volatile enough to pass through the GC column without affecting the chromatogram. Typically, highly volatile solvents like water, dimethyl sulphoxide (DMSO), N, N-dimethylformamide (DMF), and N, N-dimethylacetamide (DMAC). These solvents should not have any major components that overlap with your analytes in terms of retention time.

Chemical Inertness

The diluent should be chemically inert to the sample and the system components, meaning it should not react with the analytes, the column stationary phase, or other system parts.

Solubility of Sample Components

The diluent should ideally dissolve the analytes well enough to create a homogenous mixture. If the analytes are poorly soluble in the diluent, this could lead to uneven distribution in the headspace and inaccuracies in quantification.

Water Content

If using water as a diluent, it is crucial to consider the effect of water vapor in the headspace. High water content could lead to the formation of aqueous vapor in the headspace, which might compete with other volatile analytes for vaporization.

Typical GC-HS Diluents

Typical GC-HS diluents are water, dimethyl sulphoxide (DMSO), N, N-dimethylformamide (DMF), and N, N-dimethylacetamide (DMAC)

Applications of GC-HS in Pharmaceutical Analysis

GC-HS is widely used for the analysis of organic volatile impurities in pharmaceuticals

Conclusion

Pharmaceutical development is impossible without GC-HS. I hope this article has helped you understand GC-HS. Now you can independently develop a method on GC-HS for OVIs analysis. You may also want to check out other articles on my blog, such as GC Method adjustment and GC Method Development

FAQs

What is the GC HS method?

GC-HS is the combination of the two systems GC (gas chromatograph) and Headspace (HS). It is used for analysis of volatile impurities present in the pharmaceuticals

What is the full form of GC-HS?

Headspace Gas Chromatography

What is HS GC-MS?