Analytical chemistry by open learning


To identify residual solvents and decomposition products in Pharmaceutical compounds using static headspace gas chromatography


The gas chromatography is an analytical technique for the identification of volatile compound and quantitatively determines the mixture of pure compound by using the technique of head space sampling. The process involves preparation pure compound substance and study kinetics of reaction structural investigation and determination of physical chemical constant including stability constant of components, enthalpy, entropy and free energy of compounds.

The process weigh accurately small quantity of the solid into a vial and sealing and sealing with spectrum cap. After few minutes the sample (head space) will contain equilibrium concentration of volatile compounds present in the sample can be determined by their respective vapour pressure in which the sample withdrawing in a known volume of the vapour for injection into chromatograph by using piercing the spectrum with gas syringe in head space. It can be done under ambient or controlled elevated temperature to increase the sensitivity.

The sample containing volatile compounds vaporize partially into the gas phase and back again in to the sample after the system comes into equilibrium. The equilibrium constant under controlled condition in both concentration of sample. The sample carried out after reaching to equilibrium when the sample of two phases under static conditions

The standard can be compared with volatile compounds detected within the retention time in the head space and their concentration is proportional to those in the solid sample


  • Methanol
  • Ethanol
  • Propane-2-ol (iso-propanol)
  • Methylbenzene (Toluene)
  • Ethyl Ethanoate
  • Ethanoic Acid (Acetic acid)
  • Sample tubes large + septum caps
  • Powdered Pharmaceutical compounds A1, A2, A3, A4 and
  • Gas chromatograph with 1m Porapak QS packed column
  • Gas syringes, 100l (for standards) and 500l (for samples)

Equal volumes of methanol, ethanol, Propan-2-ol, ethyl ethanoate and ethyl benzene (0.5cm3) were mixed in a large sample tube and sealed with a septum cap. The second sample tube was containing ethanoic acid.

Two separate 0.1 g sample of compound 'A 'was weighed into two small sample tubes and 0.2 g sample of compound 'B' into third tube .the sample A tubes were sealed with septum cap immediately. Five drops of 4M NaOH was added to sample B, Tube was sealed immediately and warmed for 5Mins. Then, 5-10 drops of 4M HCl was added and resealed.

One of the sample A and Sample B tubes were placed in a beaker with sufficient water and warmed on a hot plate to maintain temperature from 60- 80 0C for 10Mins.

There is difference in magnitude of both the samples A HOT and A COLD. That is because the amount of volatile vapours released from the sample is varied on change in temperature. The increase in temperature decreases the retention time and increases the peak size and are inversely proportional.


  1. The main advantage of headspace analysis is that sampling is more easily automated and the column is not contaminated by the non-volatile components of the solution.
  2. The differences in peak sizes between the chromatographs of sample A' hot and cold because on cold the release of volatile material into atmosphere or gas stream is lesser. And as temperature is increased, the release of volatile vapours into the atmosphere increases and reduces the retention time when used for analysis.
  3. The compound identified in sample B is ACETIC ACID. Because the retention time of acetic acid used as standard is identical to the value found in SAMPLE B.
  4. The concentration of the solvent reside could be quantified on the basis of the volatility and partition coefficient of the solvents used for gas chromatography analysis.


From the experiment above, it could be concluded that GC Headspace chromatography is used in identification of residual solvents. The components in the sample A and sample B were found. The difference in magnitude was observed in sample 'A hot' and samples 'A cold'.


  1. GAS CHROMATOGRAPHY by WILLETT. Analytical chemistry by open learning.
  3. A text for pharmacy student and pharmaceutical chemists. Ed WATSON
  4. Modern practice of gas chromatography. Ed .Robertt.Grob ,Eugene F .BARR

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