Pharmazeutische Wirkstoffe und Umweltschutz

Ozonation of diclofenac in aqueous solution in the presence and absence of an *OH scavenger, tertiary butanol (t-BuOH), was studied, and the most important reaction intermediates and products were identified. The second-order O3 rate constantwas determined by competition with buten-3-ol and was found to be 6.8 x 10(5) M(-1) s(-1) at 20 degrees C. From this high rate constant, it has been concluded that O3 must initially add on the amino nitrogen. Decomposition of the adduct results in the formation of O3*- (--> *OH) and aminyl radical precursors. A free *OH yield of 30% was estimated based on the HCHO yields generated upon reaction of *OH with 0.01 M t-BuOH. Almost all diclofenac reacted when the molar ratio of O3/diclofenac was approximately 5:1 in the presence of t-BuOH and approximately 8:1 in its absence. As primary reaction products (maximum yield), diclofenac-2,5-iminoquinone (32%), 5-hydroxydiclofenac (7%), and 2,6-dichloroaniline (19%) were detected with respect to reacted diclofenac in the presence of t-BuOH. These primary products degraded into secondary ones when the O3 dose was increased. In the *OH-mediated reaction (absence of t-BuOH) small yields of 5-hydroxydiclofenac (4.5%), diclofenac-2,5-iminoquinone (2.7%), and 2,6-dichloroaniline (6%) resulted. Practically all Cl- (95%) was released in the absence of t-BuOH but only about 45% in the presence of t-BuOH at an O3/diclofenac molar ratio of 10: 1. Based on the reaction products, mechanisms that may account for the high O3 consumption during ozonation of diclofenac are suggested. For technical applications, adequate supply of O3 is needed not only to eliminate diclofenac, but also for the degradation of its potentially toxic products like diclofenac-2,5-iminoquinone and 5-hydroxydiclofenac.

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“…About 86 t/year are prescribed in Germany (1). It is metabolized mainly in the liver (2), and only a low percentage is excreted (3).…”

Section: Introductionmentioning

confidence: 99%

“…Diclofenac, a nonsteroidal antiinflammatory drug, is one of the most commonly used pain killers, clinically largely used as sodium salt. About 86 t/year are prescribed in Germany (1). It is metabolized mainly in the liver (2), and only a low percentage is excreted (3).…”

Section: Introductionmentioning

confidence: 99%

Oxidation of Diclofenac with Ozone in Aqueous Solution

Sein

Zedda

Tuerk

et al. 2008

Environ. Sci. Technol.

220

102

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“…Diclofenac is one of the most popular painkillers and anti-inflammatory agents in the world with a yearly consumption in Germany, for example, of 86 t . On the downside, it enters the environment via sewage treatment plants or runoff from fields as a consequence of artificial recharge. − There it has the potential to bioaccumulate in mussels and inhibit their growth, to harm rainbow trout, and it has been linked to the eradication of whole vulture populations .…”

Section: Introductionmentioning

confidence: 99%

C & N Isotope Analysis of Diclofenac to Distinguish Oxidative and Reductive Transformation and to Track Commercial Products

Maier

Corte²,

Nitsche³

et al. 2014

Environ. Sci. Technol.

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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.

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“…In addition to improper disposal of unused or expired medications, excretion by humans via sewage is considered a major source of pharmaceuticals entering the environment . Up to 95% of the active ingredients are excreted in an unchanged or metabolized form . Because of the compounds' stability against enzymes or acids, to allow them to reach their specific sites of action , sewage treatment plants are not able to completely eliminate these compounds.…”

Section: Introductionmentioning

confidence: 99%

Sublethal effects of the beta-blocker sotalol at environmentally relevant concentrations on the New Zealand mudsnail Potamopyrgus antipodarum

Feiner

Laforsch

Letzel

et al. 2014

Environmental Toxicology and Chemistry

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Monitoring sublethal effects of pharmaceuticals on nontarget species in aquatic environments has become an important topic in ecotoxicology, yet few studies have been conducted concerning the effects of beta-blockers on aquatic organisms. The present study investigated the effects of the beta-blocker sotalol (SOT) at 3 environmentally relevant concentrations on life-history traits of the New Zealand mudsnail Potamopyrgus antipodarum. Based on the pharmacodynamic properties of SOT, the authors hypothesized reduced numbers of embryos in the brood pouches, decelerated growth of adult snails, and smaller size of neonates, but no effect on mortality rates of adults. Contrary to the hypothesis, the total number of embryos was significantly higher after 56 d of exposure at nominal concentrations of 0.05 µg/L and 1.0 µg/L by 107% and 73%, respectively. No differences in embryo numbers were observed at earlier time-points. Therefore, the mode of action seems to be an extension of the reproductive period rather than an increase of the embryo production. Furthermore, our results indicate a hormetic dose-response relationship, because no effects were observed at the highest test-concentration (6.5 µg/L). Mortality, growth of adult snails, and neonate sizes were not affected by the beta-blocker. Given the strong influence on reproduction, the effects of sublethal concentrations of SOT and other beta-blockers deserve better consideration in ecotoxicological risk assessment.

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Pharmazeutische Wirkstoffe und Umweltschutz

Cited by 7 publications

References 47 publications

Oxidation of Diclofenac with Ozone in Aqueous Solution

Oxidation of Diclofenac with Ozone in Aqueous Solution

C & N Isotope Analysis of Diclofenac to Distinguish Oxidative and Reductive Transformation and to Track Commercial Products

Sublethal effects of the beta-blocker sotalol at environmentally relevant concentrations on the New Zealand mudsnail Potamopyrgus antipodarum

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