Identification of reaction products from reactions of free chlorine with the lipid-regulator gemfibrozil

High global consumption rates have led to the occurrence of pharmaceutically active compounds (PhACs) in wastewater. The use of chlorine to disinfect wastewater prior to release into the environment may convert PhACs into uncharacterized chlorinated by-products. In this investigation, chlorination of a common pharmaceutical, the antihyperlipidemic agent gemfibrozil, was documented. Gemfibrozil (2,2-dimethyl-5-(2,5-dimethylphenoxy)pentanoic acid) was reacted with sodium hypochlorite and product formation was monitored by gas chromatography-mass spectrometry (GC-MS). The incorporation of one, two or three chlorine atoms into the aromatic region of gemfibrozil was demonstrated using negative-ion electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (ESI-MS/MS). Further analysis using 1H nuclear magnetic resonance (NMR) spectroscopy identified the reaction products as 4′-ClGem (5-(4-chloro-2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid) 4′,6′-diClGem (5-(4,6-dichloro-2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid), and 3′,4′,6′-triClGem (5-(3,4,6-trichloro-2,5-dimethylphenoxy)-2,2-dimethylpentanoic acid), products consistent with electrophilic aromatic substitution reactions. The rapid reaction of gemfibrozil with free chlorine at pH conditions relevant to water treatment indicates that a mixture of chlorinated gemfibrozils is likely to be found in wastewater disinfected with chlorine.