Exploring Trends of C and N Isotope Fractionation to Trace Transformation Reactions of Diclofenac in Natural and Engineered Systems.

Although diclofenac ranks among the most frequently detected pharmaceuticals in the urban water cycle, its environmental transformation reactions remain imperfectly understood. Biodegradation-induced changes in 15N/14N ratios (εN = -7.1‰ ± 0.4‰) have indicated that compound-specific isotope analysis (CSIA) may detect diclofenac degradation. This singular observation warrants exploration for further transformation reactions. The present study surveys carbon and nitrogen isotope fractionation in other environmental and engineered transformation reactions of diclofenac. While carbon isotope fractionation was generally small, observed nitrogen isotope fractionation in degradation by MnO2 (εN = -7.3‰ ± 0.3‰), photolysis (εN = +1.9‰ ± 0.1‰), and ozonation (εN = +1.5‰ ± 0.2‰) revealed distinct trends for different oxidative transformation reactions. The small, secondary isotope effect associated with ozonation suggests an attack of O3 in a molecular position distant from the N atom. Model reactants for outer-sphere single electron transfer generated large inverse nitrogen isotope fractionation (εN = +5.7‰ ± 0.3‰), ruling out this mechanism for biodegradation and transformation by MnO2. In a river model, isotope fractionation-derived degradation estimates agreed well with concentration mass balances, providing a proof-of-principle validation for assessing micropollutant degradation in river sediment. Our study highlights the prospect of combining CSIA with transformation product analysis for a better assessment of transformation reactions within the environmental life of diclofenac.

C & N isotope analysis of diclofenac to distinguish oxidative and reductive transformation and to track commercial products.

Although diclofenac is frequently found in aquatic systems, its degradability in the environment remains imperfectly understood. On the one hand, evidence from concentration analysis alone is inconclusive if an unknown hydrology impedes a distinction between degradation and dilution. On the other hand, not all transformation products may be detectable. As a new approach, we therefore developed GC-IRMS (gas chromatography-isotope-ratio mass-spectrometry) analysis for carbon and nitrogen isotope measurements of diclofenac. The method uses a derivatization step that can be conducted either online or offline, for optimized throughput or sensitivity, respectively. In combination with on-column injection, the latter method enables determination of diclofenac isotope ratios down to the sub-µgL(-1) range in environmental samples. Degradation in an aerobic sediment-water system showed strong nitrogen isotope fractionation (εN = -7.1‰), whereas reductive diclofenac dechlorination was associated with significant carbon isotope fractionation (εC = -2.0‰). Hence dual element isotope analysis bears potential not only to detect diclofenac degradation, but even to distinguish both transformation pathways in the environment. In an explorative survey, analysis of commercial diclofenac products showed significant differences in carbon and nitrogen isotope ratios, demonstrating a further potential to track, and potentially even to authenticate, commercial production batches.