Inert gas sparge leads to alternate reaction pathway

The effect of sparging with an inert gas (argon) was evaluated during the investigation of the solution kinetics of an oxidation-prone amphiphilic drug containing a sulphide moiety. Samples stored with an air headspace in pH7 and 8 phosphate buffers at elevated temperatures and in the absence of light degraded to two main products, a sulphoxide and a cinnamic acid analogue. Initially, this appeared to be a sequential mechanism which could be blocked by removing oxygen. Instead, argon-sparge forced the direct degradation to the cinnamate, which was evidenced by the formation of a strong odour of sulphide. In addition, argon-sparged samples remained colourless, while those sparged with oxygen or stored with an air headspace turned yellow and had negligible odour. The half-lives for samples stored in pH 8 buffers at 93 degrees C at an initial drug concentration of 25 mg mL(-1) were 128 days (argon sparged), 86 days (air headspace), and 65 days (oxygen sparged). The results indicated that for the drug under study, sparging with an inert gas affected the mechanism as well as the rate of the reaction at elevated temperatures.