Comparison of quantitative analytical methods in headspace gas chromatography of residual solvents

The aim of this work was to compare quantitative methods used for headspace gas chromatographic analysis of residual solvents in standard aqueous solutions and to apply the methods to the analysis of medicines. We found that all three quantitative methods (external standard, ESTD; internal standard, ISTD; and standard addition, ASTD) enable determination of the total amount of solute in the equilibrated system by analysis of defined volumes of headspace gas: The results showed that the ISTD method is more precise than ESTD and ASTD when there is no strong interaction between the residual solvents and the pharmaceutical base material. When, however, there is a strong polar-polar interaction between them, the ESTD and ISTD methods give worse results than the ASTD method, because the ASTD method can eliminate the matrix effect.