Transformations of Pharmaceutical Compounds by Chlorination Processes


Mary Bedner and William A. MacCrehan

Division 839.04, CSTL

Room B162 Bldg 227, MS 8394

Phone: 301.975.4142; Fax: 301.977.0587




Many pharmaceutical compounds are continuously released into the environment and have been recognized as a potential threat due to their inherent bioactivity.  They enter the environment primarily through both treated and untreated waste, and many are therefore subject to wastewater treatment.  Wastewater treatment often utilizes chemical processing stages such as disinfection with chlorine that could transform reactive pharmaceutical compounds. 


We are currently investigating the reactivity of four pharmaceutical compounds with chlorine.  Pharmaceuticals were selected based on their previous detection in the environment and also their potential for reaction with chlorine.  The compounds include the analgesics acetaminophen and diclofenac, the antibiotic sulfamethoxazole, and the anti-hypertensive metoprolol.  The reactivity of these compounds with chlorine is being investigated using reversed-phase liquid chromatography (LC), which separates the oxidation products from the parent compound.  Products are being monitored using ultraviolet absorbance, electrochemical (EC), and mass spectrometric (MS) detection modes.  EC aids in identifying products that have oxidizing ability.  Three of the pharmaceuticals studied (diclofenac, sulfamethoxazole, and metoprolol) contain amines and might form chloramines upon reaction with chlorine.  To detect chloramine products, post-column reaction chemistry combined with the EC detection was used.  Electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) MS methods are also currently under development and have enabled tentative identifications of a number of chlorination products. 


All four pharmaceutical compounds undergo facile reaction with chlorine under the conditions of our investigation, in most cases forming multiple products that are more hydrophobic than the parent pharmaceutical (based on their LC retention characteristics).  Acetaminophen reacts with chlorine to form at least seven products, two of which have been identified as the highly toxic compounds 1,4-benzoquinone and N-acetyl-p-benzoquinone imine.  Metoprolol and sulfamethoxazole both appear to form a chloramine as one of their oxidation products.  Diclofenac forms at least five products, but it does not form a chloramine.  Ultimately, we would like to identify the oxidation products of all of these environmentally important pharmaceutical compounds.


Category: Chemistry

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