Objective-Specific Measurement Selection for Mechanistic Assessment of Pharmaceutical UVC Degradation

Background: Pharmaceutical photodegradation studies often use the same concentration data to predict compound loss and to infer the responsible reaction pathway, although these two objectives may require different measurements. Methods: We evaluated a published mechanistic model for UVC treatment of atenolol, acetaminophen, clofibric acid, and antipyrine. Morris elementary-effects screening ranked ten uncertain inputs separately for atenolol half-life and its superoxide-mediated loss fraction. Local Fisher-information analysis then compared eight candidate measurement strategies at six sampling times under 5%, 10%, and 20% assumed probe error. Results: Half-life was governed primarily by quantum yield, initial dissolved organic matter absorbance, photon intensity, and hydroxyl-radical yield, with mean absolute effects of 76.0, 73.5, 72.6, and 66.8 min, respectively. Mechanistic attribution was instead controlled by an effective radical-termination term and grouped superoxide kinetics. The parent-only Fisher matrix was poorly conditioned (8.93 x 10^7). At 10% assumed error, a six-point hydrogen peroxide series reduced the local standard deviation of log kTT,eff to 0.072 and the condition number to 158; additional parent-based strategies left the target standard deviation between 1.95 and 105. Hydrogen peroxide ranked first at all three assumed error levels. Conclusions: Measurements that improve degradation prediction differ from those that resolve photochemical mechanism. Objective-specific sensitivity analysis followed by information-based design provides a transparent method for prioritizing analytical effort in pharmaceutical degradation studies. The proposed measurements remain to be validated experimentally.