| The purpose of this thesis was to understand the reactions that pharmaceutically active compounds undergo during chlorination. In particular, this research would help to identify new chlorinated by-products, which form following the reaction of free chlorine and pharmaceutically active compounds. The scope of this thesis was limited to the following pharmaceuticals: ibuprofen, carbamazepine, naproxen, and gemfibrozil, which were selected on the basis of high occurrence in literature, distinct chromatographic separation, and high global prescriptions. The target compounds were reacted with free chlorine and analyzed for the formation of chlorinated by-products by gas chromatography-mass spectrometry. Ibuprofen and carbamazepine did not form chlorinated by-products with the analytical method used. On the other hand, naproxen formed a large number of chlorinated by-products, and gemfibrozil produced one distinct chlorinated by-product. Follow-up experiments were conducted with gemfibrozil and its identified by-product. Based on subsequent kinetic experiments, a pseudo-1st- order rate constant was calculated for gemfibrozil degradation, as 3.1 +/- 0.2 x 10-3 min -1. Negative-ion mass spectrometry and nuclear magnetic resonance were used to confirm that the structure of the gemfibrozil by-product was 5-(3-chloro-1,4-dimethylphenoxy)-2,2-dimethylpentanoic acid, as expected from an electrophillic aromatic substitution reaction. This chlorinated by-product was stable for up to fourteen days, and preliminary data indicated that the by-product was more toxic than the parent compound. Solid-phase extraction was used to determine that the formation of the chlorinated gemfibrozil by-product was greater at pH 7 than pH 8. The formation of this chlorinated by-product at pH conditions relevant to water treatment and its fast formation indicate that it will be found in environmental samples. Degradation of pharmaceuticals does not necessarily mean that environmental risk has been mitigated. |
