Vol. 7, Issue 2, Part H (2025)

The identification of volatile organic compounds (VOCs) through a preliminary extractable study and the attribution to the contact component from which they originate is one of the essential requirements of the E&L study. Polar to mid-polar VOCs demonstrate low detector sensitivity compounds compared to non-polar VOCs due to their solubility in polar solvents that restrict them from transit into headspace. Most pharmaceutical and biological formulations are aqueous; therefore, the identification of potential volatile leachable compounds becomes more challenging when the estimated Analytical Evaluation Threshold (AET) for an E&L study is at a sub-ppb level. This review article emphasises various approaches used to enhance detector sensitivity and highlights the benefits of the solvent depletion approach. Changing the phase ratio and partition coefficient are two conventional methods used to improve detector sensitivity, but they are often found to be insufficient for achieving the sub-ppb level. The introduction of hydrate-forming inorganic salts, such as Sodium sulphate anhydrous and magnesium sulphate anhydrous, which are primarily used as drying agents, played a key role in enhancing the detector sensitivity of polar to semi-polar volatile compounds by depleting the aqueous portion from the sample solution and making them freely available to the headspace for detection.