Application of LC-MS for the identification and quantification of pharmaceuticals and their transformation products during catalytic ozonation

The presence of pharmaceuticals in the environment is of concern due to their harmful effect on aquatic organisms. Because of this, it is important that they are effectively removed in wastewater treatment plants. Conventional treatment plants are unable to completely remove pharmaceuticals, so new, more effective treatment methods are needed. One promising method is catalytic ozonation. In this thesis the removal of pharmaceuticals by catalytic ozonation is investigated.

It is not enough to remove pharmaceuticals in wastewater since complete mineralization of organic compounds is very rarely achieved during water treatment. Instead, pharmaceuticals are transformed into new products. These products can even be more toxic to aquatic organisms than the parent compound. In this thesis, the transformations which takes place during ozonation are studied for four pharmaceuticals: the pain-killers ibuprofen (IBU) and diclofenac (DCF), the anti-epileptic pharmaceutical carbamazepine (CBZ), and the antibiotic sulfadiazine (SDZ).

The transformation of the pharmaceuticals was studied with the help of liquid chromatography and gas chromatography coupled to ion trap-, triple quadrupole- and time-of-flight mass spectrometry. Some of the major products were also isolated and analyzed with nuclear magnetic resonance spectroscopy (NMR). Some of the major products formed during the ozonation of the pharmaceuticals were also quantified with LC-MS or LC-UV.

All of the selected pharmaceuticals could effectively be transformed through ozonation. Catalysts either slowed down or sped up the transformation. For IBU, copper-based catalysts enhanced the transformation, while platinum-based catalysts enhanced the transformation of DCF. The transformation of CBZ was slowed down by the addition of palladium-based catalysts, while copper-based catalysts enhanced the reaction. The transformation of SDZ was slowed down by both iron-based and copper-based catalysts.

For IBU, 12 different transformation products could be detected. The structures of six of the products could be confirmed with the help of authentic samples. The main product formed resulted from hydroxylation and subsequent oxidation to a ketone. The detected products only accounted for 6 % of the transformed IBU, indicating that IBU is transformed into smaller, more polar compounds which could not be detected with LC-MS or GC-MS.

For DCF 14 different products could be detected and the structure of three of them could be confirmed with the help of reference samples. Three of the DCF products were quantified. The major product was formed from DCF via hydroxylation. Only 20 % of the transformed DCF could be accounted for.

For CBZ, 15 different products were detected. Three of the products were isolated and the structures were confirmed with NMR. CBZ was mainly transformed via a rearrangement reaction to 1-(2-benzaldehyde)-4-hydro-(1H,3H)-quinazoline-2-one (BQM), and further oxidized via direct ozonation to 1-(2-benzaldehyde)-(1H,3H)-quinazoline-2,4-dione (BQD). During non-catalytic ozonation, 74 % of CBZ was transformed into BQM and 83 % of BQM was III transformed into BQD. A significant amount of CBZ is also transformed via ringopening leading to the formation of 2,2'-azanediyldibenzaldehyde.

For SDZ, 16 different products were detected. The structure of one product was confirmed using an authentic reference samples and the structure of the major product was confirmed with NMR. SDZ was mainly transformed via a long series of steps leading to the formation of 8-nitropyrimido[1,2-a]benzimidazol-9-ol (SDZ-P15). The concentration of SDZ-P15 increased for 50 minutes, until it accounted for 30 % of the initial concentration of SDZ.