New Framework To Diagnose the Direct Disposal of Prescribed Drugs in Wastewater - A Case Study of the Antidepressant Fluoxetine.

Intentional or accidental release (direct disposal) of high loads of unused pharmaceuticals into wastewater can go unnoticed. Here, direct disposal of a pharmaceutical drug via the sewer network was identified for the first time using wastewater analysis. An irregularly high load of the antidepressant fluoxetine in raw wastewater (10.5 ± 2.4 g d(-1)) was up to 11 times greater than any other day. National prescription data revealed a predicted daily fluoxetine load for the studied treatment works to be 0.4-1.6 g d(-1). Enantio-selective analysis showed the high load of fluoxetine was present as a racemic mixture, which is typical for fluoxetine in dispensed formulations. As fluoxetine undergoes stereoselective metabolism within the body, a racemic mixture in wastewater suggests a nonconsumed drug was the major contributor of the high load. This was confirmed by its major metabolite norfluoxetine whose load did not increase on this day. Considering the most commonly prescribed formulation of fluoxetine, this increased load accounts for the disposal of ∼915 capsules. Furthermore, as fluoxetine is prescribed as one capsule per day, disposal is unlikely to be at the patient level. It is postulated that direct disposal was from a facility which handles larger quantities of the drug (e.g., a pharmacy).

[1]  Christoph Ort,et al.  Comparing illicit drug use in 19 European cities through sewage analysis. , 2012, The Science of the total environment.

[2]  S. Evans,et al.  Enantiomer profiling of high loads of amphetamine and MDMA in communal sewage: a Dutch perspective. , 2014, The Science of the total environment.

[3]  B. Peake,et al.  Disposal practices for unused medications in New Zealand. , 2009, Environment international.

[4]  Y. Picó,et al.  Occurrence and removal of drugs of abuse in Wastewater Treatment Plants of Valencia (Spain). , 2014, Environmental pollution.

[5]  Paul Griffiths,et al.  UvA-DARE ( Digital Academic Repository ) Spatial differences and temporal changes in illicit drug use in Europe quantified by wastewater analysis , 2014 .

[6]  B. Kasprzyk-Hordern,et al.  Stereoisomeric profiling of drugs of abuse and pharmaceuticals in wastewaters of Valencia (Spain). , 2014, The Science of the total environment.

[7]  Alejandro J. Ramirez,et al.  Enantiospecific sublethal effects of the antidepressant fluoxetine to a model aquatic vertebrate and invertebrate. , 2007, Chemosphere.

[8]  Akke Vellinga,et al.  Public practice regarding disposal of unused medicines in Ireland. , 2014, The Science of the total environment.

[9]  J. Parrott,et al.  Environmental risk assessment for the serotonin re‐uptake inhibitor fluoxetine: Case study using the European risk assessment framework , 2010, Integrated environmental assessment and management.

[10]  S. Evans,et al.  Determination of chiral pharmaceuticals and illicit drugs in wastewater and sludge using microwave assisted extraction, solid-phase extraction and chiral liquid chromatography coupled with tandem mass spectrometry. , 2015, Analytica chimica acta.

[11]  B. Venhuis,et al.  Success of rogue online pharmacies: sewage study of sildenafil in the Netherlands , 2014, BMJ : British Medical Journal.

[12]  Barbara Kasprzyk-Hordern,et al.  Illicit and pharmaceutical drug consumption estimated via wastewater analysis. Part A: chemical analysis and drug use estimates. , 2014, The Science of the total environment.

[13]  Christoph Ort,et al.  Sampling for PPCPs in wastewater systems: comparison of different sampling modes and optimization strategies. , 2010, Environmental science & technology.

[14]  S. Caccia Metabolism of the Newer Antidepressants , 1998, Clinical pharmacokinetics.

[15]  H. Neels,et al.  Do concentrations of pharmaceuticals in sewage reflect prescription figures? , 2015, Environmental Science and Pollution Research.

[16]  Conrad Marx,et al.  Occurrence and removal of frequently prescribed pharmaceuticals and corresponding metabolites in wastewater of a sewage treatment plant. , 2015, The Science of the total environment.

[17]  C. DeVane Pharmacokinetics of the selective serotonin reuptake inhibitors. , 1992, The Journal of clinical psychiatry.

[18]  B. Kasprzyk-Hordern,et al.  Multi-residue analysis of 90 emerging contaminants in liquid and solid environmental matrices by ultra-high-performance liquid chromatography tandem mass spectrometry. , 2016, Journal of chromatography. A.

[19]  Á. Ríos,et al.  Use of toxicity assays for enantiomeric discrimination of pharmaceutical substances. , 2009, Chirality.

[20]  Athanasios S Stasinakis,et al.  Is there a risk for the aquatic environment due to the existence of emerging organic contaminants in treated domestic wastewater? Greece as a case-study. , 2015, Journal of hazardous materials.

[21]  Christian G. Daughton,et al.  Illicit Drugs in Municipal Sewage: Proposed New Nonintrusive Tool to Heighten Public Awareness of Societal Use of Illicit-Abused Drugs and Their Potential for Ecological Consequences , 2001 .

[22]  Lee E. Brown,et al.  Global Synthesis and Critical Evaluation of Pharmaceutical Data Sets Collected from River Systems , 2012, Environmental science & technology.

[23]  D. A. Barry,et al.  Temporal dynamics of antibiotics in wastewater treatment plant influent. , 2013, The Science of the total environment.

[24]  S. Kapur,et al.  Comprar The Maudsley Prescribing Guidelines, 10th Edition | Shitij Kapur | 9781841846996 | Informa Healthcare , 2009 .

[25]  M D Devous,et al.  Comparison of SPECT applications in neurology and psychiatry. , 1992, The Journal of clinical psychiatry.

[26]  A. Küster,et al.  The CHMP guideline on environmental risk assessment of medicinal products for human use: Three years of regulatory experience , 2009 .

[27]  N. Farid,et al.  Clinical Pharmacology and Pharmacokinetics of Fluoxetine: A Review , 1988, British Journal of Psychiatry.

[28]  B. Peake,et al.  Disposal practices for unused medications in New Zealand community pharmacies. , 2011, Journal of primary health care.

[29]  S. Kapur,et al.  The Maudsley Prescribing Guidelines , 2009 .

[30]  M. Gardner,et al.  Performance of UK wastewater treatment works with respect to trace contaminants. , 2013, The Science of the total environment.