Monitoring the Trace Levels of Free Sulfate Release to Terminate a Depolymerization Reaction Using ATR-FTIR

The synthesis of a pharmaceutical product involves a critical depolymerisation reaction which determines the final product quality attributes. Hence, termination of this reaction at the desired end point is utmost important to achieve a consistent product with required specifications. However, monitoring this reaction is challenging due to low chemical specificity of the reaction species involved. In this work, we developed a novel PAT method based on ATR-FTIR combined with chemometrics to monitor this reaction. To achieve this, we first identified the reaction mechanism and the rate-controlling step and monitored the reaction progress by tracking the free sulfate release which forms as a by-product during the reaction. The PAT method has been validated at lab and kilo scales and subsequently transferred to the plant and successfully implemented at manufacturing scale.