Synthesis of multiply deuterated 3- and 21-monosulfates of allo-tetrahydrocorticosteroids as internal standards for mass spectrometry

► We synthesized the 3- and 21-monosulfates of multiply deuterated 5α-tetrahydrocorticosteroids. ► Exchange reaction of the 5α-3- or -11-ketosteroids with NaOD in MeOD followed by NaBD4 was employed. ► 3β-Hydroxy group was epimerized into 3α configuration by Walden inversion. ► Sulfation of C-3 and C-21 hydroxy groups was attained by treatment with SO3-TMA complex. ► The isotopic purity of labeled compound was enough high to use them as a internal standard in LC/MS.