Full evaporation headspace gas chromatography with thermal conductivity detection for the direct determination of water in solid pharmaceutical bulk products

Headspace gas chromatography (HS-GC) has the potential to be used for water determination in pharmaceutical products. In this article, its use for the determination of water in solid samples is explored without the need of dissolution by means of the full evaporation technique (FET). This way, water is thermally removed from a small amount of sample which is directly weighed in the vial. This simplifies considerably the method since no diluent has to be searched and HS saturation is avoided. Blank corrections were performed to compensate for atmospheric moisture variation. Moreover, the performance of mass spectrometry (MS) and thermal conductivity detection (TCD) was compared. The method showed excellent figures of merit when working with TCD, such as R2 0.99 and RSD < 5% for each level of the calibration curve. Eight samples were carefully studied at different equilibration temperatures to find the optimal working conditions for each case and the results were compared to the ones obtained by Karl Fischer titration (KFT). Both methods showed restrictions and proper case by case optimization/validation turned out to be mandatory. Hyphenation with a flame ionization detector (FID) in series with the TCD showed the benefit to be useful for testing residual solvents (RS) simultaneously. (c) 2021 Elsevier B.V. All rights reserved.