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Abstract: In this paper, three different HPLC methods for the quantification of thalidomide in tablets were developed and compared. The comparison of a conventional method at 30°C with two high-temperature methods at 180°C showed equal results. Using high-temperature HPLC (HT-HPLC), faster analysis times could be achieved. We have also focused on analyte stability and could show that the stationary phase has a pronounced effect on the on-column degradation of thalidomide at high temperatures. Virtually no degradation occurs if a polystyrene divinylbenzene column is used, whereas thalidomide is completely degraded at 180°C when a carbon clad zirconium dioxide column is used. [Copyright &y& Elsevier]