This work studied the short-term stability of 6α-chloro-testosterone (6-CT), 6β-bromo-androstenedione (6-BrAED) and 6-oxo-androstenedione (6-oxo-AED) in methanol (MeOH) and dimethylsulfoxide (DMSO) solutions by gas and liquid chromatography coupled to mass spectrometry. Solutions of 6-CT, 6-BrAED and 6-oxo-AED were prepared in MeOH and DMSO. They were stored at room temperature, +4°C and -20 °C. Measurements were made at 0, 7, 30, 60 and 90 days after solutions preparation, by liquid chromatography-tandem mass spectrometry and gas chromatography-high resolution mass spectrometry. Although the degradation of 6-CT and 6-BrAED was extensive, the most notable result was that the higher degradation occurred in DMSO instead of MeOH. The interaction of DMSO with halogenated species and secondary hydroxyl groups favored the degradation of these compounds by forming chemically related species. No degradation of 6-oxo-AED in either MeOH or DMSO was observed. Pronounced degradation of the 6-CT and 6-BrAED, during the derivatization reaction for the gas chromatography-mass spectrometry analysis was observed. Because of the acidic condition of the reaction and depending on the reactant, it was favored the loss of the halogen molecule or the dehydration reaction to form the unsaturated (Δ6) steroid derivative. Our finding suggests to take duly into account the possibility of degradation processes when performing quantitative determination of 6-CT, 6-BrAED and 6-oxo-AED by chromatographic-spectrometric techniques based on the use of reference solutions stored for sufficiently long times.