Field collection and laboratory-controlled exposure studies are critical to establishing the toxicity and long-term consequences of aquatic plastic debris and their associated chemical contaminants (e.g. plasticisers) on organisms. A critical aspect of these studies relates to the separation and retrieval of plastics from biological sample matrices using a variety of extraction techniques. Popular separation methods for micro and nano-size plastics involve prolonged, high temperature treatment with a range of alkali, oxidative and/or acidic chemical reagents (e.g. 60oC with nitric acid). While these techniques offer a more efficient and robust means of sample clarification, their strongly acidic and oxidative properties have been associated with physical damages, enhanced polymer reactivity and fragment deterioration. Considering many identification and characterisation techniques post-recovery involve qualitative visual assessment and comparative spectroscopy, it is imperative that the chemical and physical characteristics of the plastic polymers are not impacted during chemical digestion. Here, we apply an analytical approach to characterise and quantify the reactivity and degradative impacts of common chemical digestion methods on polystyrene-based microplastics, chosen because of their high prevalence in aquatic environments globally. Based on these results, chemical digestion methods will be ranked to determine their appropriateness for microplastic separation, and recommendations for updates to future protocols will be offered.