Evaluation of N-Oxide Venlafaxine Transformation Product Kinetics During Ozonation

Ines Zucker, School of Mechanical Engineering and Hydrochemistry, Geography and the Environment, Tel Aviv University, Tel Aviv, Israel
Alon Riani,School of Mechanical Engineering and Hydrochemistry, Geography and the Environment, Tel Aviv University, Tel Aviv, Israel
Dror Avisar, Hydrochemistry, Geography and the Environment, Tel Aviv University, Tel Aviv, Israel
Hadas Mamane, School of Mechanical Engineering, Tel Aviv University, Tel Aviv, Israel

Venlafaxine is an antidepressant found in several environmental samples at the concentrations ranged from several ng/L level to as high as 2 μg/L. Similar venlafaxine concentrations were found to impact tissue metabolic capacities and may compromise the adaptive responses to an acute stressor in non-target aquatic animals. Venlafaxine degradation was reported by advanced oxidation processes such as UV/H2O2 and ozonation. Ozonation of wastewater from pharmaceutical industry revealed the formation of N-oxide-venlafaxine as the major product. Estimations indicate that N-oxides are not necessarily better removed in biological post-treatment. However, further research on N-oxide-venlafaxine biological activity and degradation by ozonation and post-ozonation treatments were not reported to the best of our knowledge. This systematic study includes mass balance evaluation to elucidate the major pathway during ozonation. Kinetic study on N-oxide-venlafaxine formation and degradation in wastewater effluent ozonation was demonstrated.

N-oxide-venlafaxine and venlafaxine standards (>99% purity) were obtained from Holland Moran. Bench-scale ozonation experiments were conducted in 50 mL stirred glass vessels. Ozone stock solution (~60 mg/L) was prepared by continuously bubbling ozone gas, produced from an oxygen fed generator (up to 4 g/h, BMT 802N, Germany), in a glass reactor filled with chilled deionized water. The target compounds were detected and quantified by HPLC (HPLC-Agilent 1100 series; ACE-RP phenyl column 2.5 mm×250 mm) equipped with a UV diode array detector and a mass spectrometer (QTof MS, Waters). Competition kinetics were used to determine the second order rate constant for the reaction of N-oxide-venlafaxine with ozone (1/M s) using bezafbrate as a reference compound and with hydroxyl radicals with carbamazepine.

The formation of N-oxide-venlafaxine was observed at different venlafaxine-spiked waters (deionized-water, synthetic and municipal wastewater effluents) and different pH values. The maximum yield (i.e. N-oxide-venlafaxine to venlafaxine concentration ratio) was observed in ozone dose of 0.6-0.7 mg O3/ mg DOC and varied between 10 and 77 %. The difference might be the result of either promoters or scavengers of hydroxyl radicals (e.g. DOC, pH, nitrate and carbonates). For example, increasing pH from 7.1 to 9.0 during ozonation of venlafaxine-spiked deionized water resulted in increased yield from 60 to 76 %. Correlation between hydroxyl radical's exposure and the maximum yield enabled prediction of N-oxide-venlafaxine formation. Further reaction of the N-oxide-venlafaxine product with ozone was also observed, which eliminated at a dose of 1.5 mg O3/mg DOC. Rate constants of N-oxide-venlafaxine reaction with ozone and with hydroxyl radical were measured to be 308 1/M s and 5.34∙109 1/M s, respectively. Hence, the main mechanism for N-oxide-venlafaxine degradation is hydroxyl radical chain-reactions. Based on the findings, prediction of venlafaxine and N-oxide-venlafaxine concentrations following ozonation was enabled. Evaluation of data obtained from ozonation of secondary effluent may confirm this prediction. 

N-oxide-venlafaxine was approved to be the major product from ozonation of venlafaxine. The maximum yield was found to vary between 10 to 76 %, depending on hydroxyl radical promoters/scavenger presence. Prediction of venlafaxine and its main transportation product concentrations during ozonation was enabled. This ongoing research attempts to evaluate the biodegradability of N-oxide-venlafaxine as well as its toxicity and impact on the aquatic environment. 

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