Seasonal Monitoring of Cardiovascular and Antiulcer Agents' Concentrations in Stream Waters Encompassing a Capital City.

Nowadays monitoring pharmaceutical residues from surface waters is a widespread analytical task. Most of the studies are conducted from river waters or sewage treatment plants and mainly in Western Europe or North America. Such studies are seldom published from Eastern Europe, especially from stream waters, even though the prescription and consumption patterns of drugs as well as wastewater treatment procedures are very dissimilar. In Hungary the active substance of the most often prescribed drugs are cardiovascular and antiulcer agents. Hence in our study compounds belonging to these two groups were seasonally monitored in two main streams encompassing the Buda side of the Hungarian capital city and flowing into the Danube. To obtain data on the occurrence, fate, and seasonal variation of the compounds, samples were taken from altogether eleven points located near wastewater treatment plants and confluences. The results gave no identifiable pattern in the seasonal variation of concentrations but the contribution of the tributaries and wastewater treatment plants could be followed as expected. From the runoff corrected estuary concentrations the annual contribution of these streams to pharmaceutical pollution of the Danube could be estimated to be in excess of 1 kilogram for atenolol, famotidine, metoprolol, ranitidine, and sotalol.

Identification of phase I metabolites of cardiovascular and anti-ulcer drugs in surface water samples with liquid-chromatography-mass spectrometry methods.

In our study we have identified phase I metabolites of cardiovascular and anti-ulcer agents with the application of predictive multiple reaction monitoring (pMRM) methods with liquid-chromatography-triple-quadrupole mass spectrometry (LC-QQQ-MS) in surface water samples. Targeted accurate mass spectrometry measurements were also carried out for confirmation with liquid-chromatography-time-of-flight mass spectrometry (LC-TOF-MS). pMRM followed by a targeted accurate mass spectrometry measurement can provide a sound basis for the selection of metabolites to be included in analytical methods for the investigation of environmental load of pharmaceuticals. Using LC-QQQ-MS twenty-one metabolites could be identified with two independent transitions at the same retention time and six of them could also be confirmed with LC-TOF-MS.

Determination of antihypertensive and anti-ulcer agents from surface water with solid-phase extraction-liquid chromatography-electrospray ionization tandem mass spectrometry.

Pharmaceuticals are emerging contaminants in surface water and they must be measured to follow their effects on the aquatic environment. We developed a solid-phase extraction and liquid chromatography-electrospray ionization tandem mass spectrometry (SPE-LC-ESI-MS/MS) method for the determination of twenty-six pharmaceutical compounds - which belong to antihypertensive and anti-ulcer agents - from surface water samples. The selection of pharmaceuticals was based on usage frequency in Hungary. During method development Oasis HLB, SampliQ Polymer SCX and Si-SCX SPE cartridges were tested. As LC eluent ammonium formate, ammonium acetate buffers at pH 3 and 5 were investigated and for quantitation both matrix-matched and internal standard calibration was used. For matrix effect assessment post-extraction spike method was applied which can separate the extraction efficiency from ion suppression for better determination of recovery. Method detection limits (MDLs) varied between 0.2 and 10 ng/L. Precision of the method, calculated as relative standard deviation (RSD), ranged from 0.2 to 14.6% and from 1.2 to 22.4% for intra- and inter-day analysis, respectively. The method was applied to analyze Danube water samples. Measured average concentrations varied between 2 and 39 ng/L for eleven compounds and another one could be detected under LOQ.

Determination of phenols and chlorophenols as trimethylsilyl derivatives using gas chromatography-mass spectrometry.

A rapid and simple method is described for the simultaneous determination of 6 phenols (phenol, o-, m-, p-cresol, catechol and resorcinol) and 19 chlorophenols (all mono-, di-, tri-, and tetrachlorophenol isomers and pentachlorophenol) present in aqueous samples. The method is based on derivatization with trimethylsilyl-N,N-dimethylcarbamate (TMSDMC). In contrast to other derivatization agents, TMSDMC instantaneously reacts with the phenolic compounds at room temperature and no further sample processing is necessary prior to instrumental analysis. The determination of the derivatives was performed by capillary gas chromatography-mass spectrometry (GC-MS). The stability of the most instable trimethylsilyl derivative (pentachlorophenol) was studied using different excess levels of the derivatization reagent. The derivatization method was tested on spiked water samples preconcentrated by solid phase extraction on Isolute ENV+ cartridge. The overall method gave detection limits of 0.01-0.25 microg/L for all compounds and < 0.05 microg/L for 17 of them.