Synthesis of 3- and 21-monosulfates of [2,2,3β,4,4-2H5]-tetrahydrocorticosteroids in the 5β-series as internal standards for mass spectrometry

► We synthesized the 3- and 21-monosulfates of pentadeuterated 5β-tetrahydrocorticosteroids. ► Exchange reaction of the 5β-3-ketosteroids with NaOD in CH3OD followed by NaBD4 was employed. ► Sulfation of C-3 and C-21 hydroxy groups was attained by treatment with SO3-TMA complex. ► The isotopic purification of the labeled compounds as [2H5]-form were more than 95 atom% D. ► The labeled compounds can be used as internal standards in LC/MS assays.