Currently, there are no analytical methods available in the literature that can simultaneously separate and quantitate residual levels of acetone, methylene chloride, n-butyl ether and dimethylsulfoxide in Betamethasone valerate active pharmaceutical ingredient (API). This paper describes the development and validation of a simple, efficient, accurate and robust static headspace gas chromatography method for the determination of high and low boiling residual solvents, namely acetone, methylene chloride, n-butyl ether and dimethylsulfoxide, in Betamethasone valerate API. This method has been demonstrated to be accurate, linear, precise, reproducible, specific and robust for its intended purpose. Quantitation limits (QL) for acetone, methylene chloride and n-butyl ether are 20 ppm (20 μg/g of API) and 50 ppm (50 μg/g of API) for dimethylsulfoxide. Several other APIs (Loratadine and a few other corticosteroid compounds) were analyzed using the conditions of this method to evaluate and assess the versatility of this method for the purpose of residual solvents analysis for a wide range of APIs. The results of this evaluation strongly indicates that this method can be readily used (as-is or with minor modifications) to determine both low and high boiling residual solvents present in a wide range of APIs.