Combustion-related solid particles are known to potentially have adverse effects on human health. In order to enhance further our understanding of how such particles trigger biological responses in humans, it is crucial to ensure that these particles are specifically collected, and are subsequently properly characterized. To separate the solid particles from an aerosol which contain also gases and liquid droplets, a methodology using a Dekati thermo-denuder operated at 300 °C was established. The current work addresses the performance of the method by assessing its average removal efficiency based on pre-determined aerosol average penetration values for model solid particles and liquid droplets. The solid particle average penetration, or the so-called transmission efficiency, was measured to be 79.4 ± 7.3% based on the aerosol wall losses. Although penetration is size-dependent, in the current work it was assumed that poly-disperse dry NaCl particles were a good surrogate to evaluate the equipment average wall losses of combustion-related fine solid particles. To assess the ability of the thermo-denuder to remove liquid droplets from aerosols, aqueous solutions of propylene glycol and glycerin were nebulized. The largest penetration value was measured to be 2.7 ± 1.0%. As a result, the methodology limit of detection was calculated to be 3.7% and the lower limit of quantification (LLOQ) 11.1%. Moreover, further experiments were conducted to ensure that liquid-coated solid particles could be distinguished from non-evaporated droplets to avoid data misinterpretation. To this end, ∼ 70 nm-NaCl particles were coated with glycerin reaching a size diameter of the order of a micron. The experiments showed that the layer of glycerin-coated NaCl was removed entirely when the aerosol passed through the thermo-denuder for the submicron size range. As an application of the methodology, the 3R4F reference cigarette mainstream smoke and Tobacco Heating System 2.2 (THS 2.2) mainstream aerosol were tested in the thermo-denuder. The data demonstrated that for 3R4F mainstream smoke, solid particles or high boiling point droplets were quantified far above the LLOQ. In contrast, for THS 2.2 mainstream aerosol, the penetration overlapped the LLOQ within the range of experimental uncertainty. In the current work, no combustion-related particles were detected or observed when using THS2.2, and this confirms former data published on this subject.