The Transport and Fate of Fluoxetine Hydrochloride, Diazepam and their Human Metabolites in Sewage Sludge-Amended Soil

Clare H. Redshaw

PhD – September 2007

School of Earth, Ocean and Environmental Sciences, University of Plymouth, Plymouth, U.K.

in collaboration with

AstraZeneca, Brixham Environmental Laboratory

The European Union (EU) banned disposal of sewage sludge (SS) at sea in 1998. Since that time the application rate of SS to land has risen significantly and is set to rise further. Fifty-two percent of SS was disposed to land in the UK in 2000. Land application is thus possibly an important transport route for SS-associated organic chemicals into the environment.

There are now over 3000 different pharmaceutical ingredients in use in the EU and the last decade has also seen an increase in reports of pharmacologically active compounds in the environment (e.g. in watercourses, open ocean, soil). Regardless of this there is still a significant lack of knowledge as regards the transport and fate of pharmaceuticals in the environment, particularly in soils. The present project therefore investigated the biotic fate of the selective serotonin re-uptake inhibitor (SSRI), Prozac® (Fluoxetine HCl), and the 1,4-benzodiazepine, Valium® (Diazepam) and their major human metabolites Norfluoxetine HCl, Temazepam, Oxazepam and Nordiazepam in a UK SS-amended soil.

Extraction techniques, such as solid phase extraction, for the analytes from a range of matrices (water, soil and plant material) were developed, which allowed subsequent analysis using developed high performance liquid chromatography – electrospray ionization – multistage mass spectrometry (HPLC-ESI-MSn) techniques. Ratio calibration using deuterated internal standards allowed the generation of quantitative data. The pharmaceuticals were found to be resistant to biodegradation in both liquid culture studies (60 days), and even after prolonged exposure in SS-amended soil (>200 days; Fluoxetine HCl only). Oxazepam was the only 1,4-benzodiazepine studied which underwent biotic transformation (~ 80%) in liquid culture studies. Evidence to support the theory that the transformation product seen was a 1,4-benzodiazepine tautomer, is presented.

Results of what is believed to be one of the first examples of research into pharmaceutical uptake by plants are presented. In a preliminary tissue culture study the translocation of Fluoxetine HCl into Brassica stems (5% uptake) and leaves (3% uptake) confirmed that plant uptake of some pharmaceuticals may be a potential transport route in the environment. The stability of the pharmaceuticals under environmentally relevant conditions has implications for the consequent accumulation in SS-amended soils and possible subsequent uptake into plants grown on the soils.

© 2006 by C.H. Redshaw. All Rights Reserved

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