High-resolution MS and MS(n) investigation of ozone oxidation products from phenazone-type pharmaceuticals and metabolites.
Phenazone-type pharmaceuticals, such as aminopyrine, metamizole, phenazone and propyphenazone, are widely used analgesics that have been detected in wastewater treatment plant effluents in μg L(-1) concentrations. Acetamido antipyrine (AAA) and formyl aminoantipyrine (FAA) - the main metabolites of aminopyrine and metamizole - have also been detected in sub μg L(-1) concentrations in environmental water bodies and in resources used to produce drinking water, suggesting their highly persistent character. In this study phenazone, propyphenazone, AAA and FAA were treated with ozone under laboratory conditions and 17 degradation products were identified by an elucidation approach based on high-resolution mass spectrometry (LTQ Orbitrap). Typical oxidation of carbon-carbon double bonds by ozone was observed among other mechanisms of ring opening. It was demonstrated that reactivity of these compounds with ozone is high (rate constants kO3 ranging from 6.5×10(4) to 2.4×10(6) M(-1) s(-1)). The toxicity of the degradation products from ozonation was estimated by quantitative structure-activity relationships (QSAR). It was shown that, when the carbon-carbon double bond is partially oxidized to an epoxy, the toxicity towards fish and daphnids is higher than that of the parent compound. By further oxidizing the molecules, a common degradation product - 1-acetyl-1-methyl-2-phenylhydrazide (AMPH) - was also found to be more toxic than its parent compounds, which is of concern since this compound has previously been reported in environmental waters.
KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Pharmaceutical Analysis, Herestraat 49, 3000 Leuven, Belgium.
Maxime
M
Favier
KU Leuven, Department of Chemical Engineering, Process and Environmental Technology Lab, Jan Pieter De Nayerlaan 5, 2860 Sint-Katelijne-Waver, Belgium.
Raf
R
Dewil
KU Leuven, Department of Chemical Engineering, Process and Environmental Technology Lab, Jan Pieter De Nayerlaan 5, 2860 Sint-Katelijne-Waver, Belgium.
Kwinten
K
Van Eyck
KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Pharmaceutical Analysis, Herestraat 49, 3000 Leuven, Belgium.
Ann
A
Van Schepdael
KU Leuven, Department of Pharmaceutical and Pharmacological Sciences, Pharmaceutical Analysis, Herestraat 49, 3000 Leuven, Belgium. Electronic address: deirdre.cabooter@pharm.kuleuven.be.
Deirdre
D
Cabooter
D000700:Analgesics / Q000032:analysis; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry; D060766:Drinking Water / Q000032:analysis / Q000737:chemistry*; D004784:Environmental Monitoring / Q000379:methods*; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D010126:Ozone / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship; D014874:Water Pollutants, Chemical / Q000032:analysis* / Q000737:chemistry
D000700:Analgesics; D060766:Drinking Water; D014874:Water Pollutants, Chemical; D010126:Ozone; C009077:propyphenazone; D000983:Antipyrine
Degradation products; Ozonation; Pharmaceuticals; Pyrazolone; QSAR; Wastewater