This investigation into the light isomerization of tropolone was initiated after a method for determining residual tropolone in the bulk drug substance (BDS) of a therapeutic monoclonal antibody was developed and validated at our laboratory. This method, developed at a client’s request, required a detection limit of 50 parts per billion (ppb) in the BDS to meet their regulatory requirements. The method was developed using liquid chromatography and tandem mass spectrometry (LC/MS/MS) because of the selectivity and sensitivity of the technique when using selective reaction monitoring (SRM). During development, however, it was discovered that only after creating a photoisomer of tropolone could successful separation, detection, and quantitation of tropolone be achieved. During validation, the method showed good performance…