Photolysis Products of Fluorinated Pharmaceuticals: A Combined Fluorine Nuclear Magnetic Resonance Spectroscopy and Mass Spectrometry Approach

Abstract

The aqueous photolysis of four pharmaceuticals with varying fluorinated functional groups was assessed under neutral, alkaline, advanced oxidation, and advanced reduction conditions with varying light sources. Solar simulator quantum yields were 2.21 × 10‐1 mol Ei‐1 for enrofloxacin, 9.36 × 10‐3 mol Ei‐1 for voriconazole, and 1.49 × 10‐2 mol Ei‐1 for flecainide. Florfenicol direct photolysis was slow, taking 150 hours for three degradation half‐lives. Bimolecular rate constants between pharmaceuticals and hydroxyl radicals were 109 ‐ 1010 M‐1s‐1. Using a combined quantitative 19F‐NMR and mass spectrometry approach fluorine mass balances and photolysis product structures were elucidated. Enrofloxacin formed a variety of short‐lived fluorinated intermediates that retained the aryl F motif. Extended photolysis time led to complete aryl F mineralization to fluoride. The aliphatic F moiety on florfenicol was also mineralized to fluoride, but the resulting product was a known antibiotic (thiamphenicol). For voriconazole, the two aryl Fs contributed more to fluoride production compared to the heteroaromatic F, indicating higher stability of the heteroaromatic F motif. The two aliphatic CF3 moieties in the flecainide structure remained intact under all conditions, further supporting the stability of these moieties found in per‐ and polyfluoroalkyl substances (PFAS) under a variety of conditions. The advanced treatment conditions generating hydroxyl radical or hydrated electron accelerated the degradation, but not the defluorination, of flecainide. The combination of 19F‐NMR and mass spectrometry proved powerful in allowing product identification of fluorinated products and verifying the functional groups present in the intermediates and products. The results found in this study will aid in the understanding of which fluorinated functional groups should be incorporated into pharmaceuticals to ensure organofluorine byproducts are not formed in the environment and help determine the water treatment processes that effectively remove specific pharmaceuticals and more generally fluorinated motifs.

Fluorinated Pharmaceutical and Pesticide Photolysis: Investigating Reactivity and Identifying Fluorinated Products by Combining Computational Chemistry,19F NMR, and Mass Spectrometry

“…Experimental results from photolysis of sulfoxaflor, penoxsulam, fluoxetine, TFM, flecainide, florasulam, voriconazole, and fluroxypyr, including 19 F NMR spectra and LC-HRMS product identification, were used from our previous studies. − , The photolysis in our prior studies was performed with a mercury vapor lamp, solar simulator, and LEDs with 255, 275, 308, 365, and 405 nm peak wavelengths. Detailed methodology for photolysis is available in the prior works.…”

“…The most common method used for identification of fluorinated degradation products of pesticides and pharmaceuticals is liquid chromatography with nontargeted high resolution mass spectrometry (LC-HRMS) . It was reported that using only LC-HRMS to quantify fluorinated compounds can result in fluorine mass balances falling short, with up to 90% of fluorine being unaccounted for. − Recent studies on fluorinated product formation and identification during photolysis and advanced treatment processes have reported more complete product identification by complementing LC-HRMS with quantitative 19 F-nuclear magnetic resonance spectroscopy (NMR) analysis. − ,, An NMR spectrum contains all fluorinated product peaks, and the chemical shifts provide insight into the identity of the functional group and its chemical environment. With the broad range of fluorine NMR shifts (∼400 ppm) and the 100% abundance of 19 F isotope of fluorine in the environment, 19 F NMR has been reported to be a highly suitable method to detect fluorinated compounds and products .…”

“…Experimental studies have shown differences in the extent of defluorination from different fluorine motifs . While Aryl or Het-F groups are generally not a concern with respect to stable fluorinated byproducts via photolysis, CF 3 groups have been shown to form TFA along with persistent products retaining the CF 3 groups. − Previous studies on photolysis have reported that Het-CF 3 and Aliphatic-CF 2/3 motifs are retained in the product structures. ,− An increased application of heteroaromatic fluorine motifs in compounds due to their improved metabolic stability coupled with the environmental stability (and retention) of Het-CF 3 motifs in surface waters, drinking waters, and wastewaters upon photolysis and advanced treatment conditions could ultimately lead to an unparalleled increase in persistent and stable fluorinated byproducts in the environment. , …”