Accurate determination of platinum group elements (PGEs) in active pharmaceutical ingredients (APIs) is critical due to stringent regulatory requirements and the potential toxicological effects of these elements. In this study, a microwave-assisted wet digestion (MAWD) method was developed to allow interference-free determination of PGEs, including Os, in APIs by inductively coupled plasma mass spectrometry (ICP-MS). Five widely used API samples were selected and a study of interferences was performed. The evaluated conditions included the composition of the digestion solution, and sample mass. The calibration and washing solution mediums were also evaluated: 5% HCl solution or a stabilizing solution (composed of acetic acid, thiourea and ascorbic acid). Furthermore, carbon interference (up to 2000 mg L-1 of C), which is critical for PGE determination by ICP-MS, was evaluated, and it was observed that C concentrations higher than 800 mg L-1 caused interferences for PGE determination, with the exception of Os. The method was validated according to the United States Pharmacopeia (USP). The optimized conditions for the proposed MAWD method were 500 mg of sample and a mixture of HNO3+HCl (1+1, 6 mL) as digestion solution. The 5% HCl solution was suitable for the determination of all PGEs, except for Os. In the case of Os, the stabilizing solution, added to samples, blanks, standards, and as washing solution, was necessary for its quantitative determination. The proposed procedure allowed quantitative PGE recoveries, including Os, using an efficient and relatively simple sample preparation method based on MAWD. Furthermore, the limits of quantification were suitable for PGE determination according to USP requirements.