Transformations of Pharmaceutical Compounds by Chlorination Process=
es
Mary Bedner= and William A. MacCrehan
Division 83= 9.04, CSTL
Room B162 B= ldg 227, MS 8394
Phone: 301.= 975.4142; Fax: 301.977.0587
Email: mary.bedner@nist.gov
Many pharmaceutical compounds are continuously release= d 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 ar= e therefore subject to wastewater treatment. Wastewater treatment often utilizes chemical processing stages such as disinfection wi= th chlorine that could transform reactive pharmaceutical compounds.
We are currently investigating the reactivity of four pharmaceutical compounds with chlorine.&nb= sp; Pharmaceuticals were selected based on their previous detection in t= he environment and also their potential for reaction with chlorine. The compounds include the analgesi= cs 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 studi= ed (diclofenac, sulfamethoxazole, and metoprolol) contain amines and might form chloramines upon reaction with chlorine.&n= bsp; To detect chloramine products, post-column reaction chemistry combin= ed with the EC detection was used. Electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) MS met= hods are also currently under development and have enabled tentative identificat= ions of a number of chlorination products.
All four pharmaceutical compounds undergo facile react= ion with chlorine under the conditions of our investigation, in most cases form= ing 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 oxida= tion products. Diclofenac forms at= least five products, but it does not form a chloramine. Ultimately, we would like to ident= ify the oxidation products of all of these environmentally important pharmaceut= ical compounds.
Category: Chemistry
Note: I = am not a Sigma Xi member.