Sublimation is the direct transformation of a solid to a gaseous state. For instance, at standard pressure and room temperature, solid carbon dioxide sublimes to gaseous carbon dioxide. The phase diagram depicts the conditions required for sublimation. This process occurs at the solid-gas phase boundary and is not observed above the triple point of the substance. The reverse of sublimation is called deposition, where a gaseous substance condenses directly into a solid. Sublimation and deposition can both be used to separate an analyte from interferents.

In simple sublimation, a solid sample is heated in a beaker covered with an inverted watch glass acting as the secondary surface. The analyte sublimes into a gas, and then cools to a solid again when it meets the watch glass. For successful purification, the sublimation temperature must be high enough to ensure high vapor pressure, but low enough to avoid either melting or decomposing the substance. Iodine is an example of a substance amenable to purification by simple sublimation.

If the sample is sensitive to heat, low-temperature sublimation techniques such as freeze-drying (also known as lyophilization) can be used. These techniques are often applied to dehydrate the desired material. Here, the sample is frozen using an ultra-low-temperature mixture (dry ice/acetone), and placed in a vessel attached to a vacuum pump. The ice in the sample sublimes to water, leaving behind the desired, cryo-desiccated product. Lyophilization is used extensively in purifying enzymes for use in biochemistry, molecular biology, and food preservation.