The determination of residual solvents in active substances, excipients, and medicines is mandatory during release testing and advisable throughout the entire drug manufacturing process. Official regulatory bodies recommend headspace-gas chromatography (HS-GC) as the analytical procedure of choice for identification and control of residual solvents in pharmaceuticals. The official headspace-gas chromatography methods assume that the sample can be made into a homogenous solution, which is then analyzed. However, not all compounds can be easily dissolved. A recently presented thermal desorber-gas chromatography (TD-GC) method, developed by the Pharmaceutical Analysis laboratory of KU Leuven and successfully used as an alternative way to determine residual solvents in complex matrices, was adapted and applied to determine residual solvents in different types of modified cellulose beads. Ideally, thermal desorption should be calibrated using gas-phase standards. However, in practice, gas-phase standards are expensive and difficult to obtain, so calibration is routinely done using liquid standards. Calibration becomes critical when thermal desorption is used for direct thermal extraction of residual solvents from solid samples because then the adsorption and desorption pathways of residual solvents in the sample and the reference differ significantly. Inline (ILC) and offline (OLC) liquid calibration were explored as potential calibration methods. After optimization of both methods, offline liquid calibration showed poorer recovery and precision compared to inline liquid calibration. So, inline liquid calibration was chosen as the preferred calibration method for this kind of analysis.