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Municipal wastewater has been examined for steroids, beta(2)-agonists, stimulants, diuretics, and phosphodiesterase type V inhibitors (PDE type V inhibitors), which are "dual-use-drugs" applied either as anabolic, doping, and lifestyle drugs or for treatment of diverse diseases. To identify their origin, fitness centre discharges under suspicion of being point sources and sewage-treatment plant feed and effluents were sampled and concentrations determined. Sensitive and selective methods for determination and quantification based on solid-phase extraction (SPE) followed by high-performance liquid chromatography-high resolution mass and tandem mass spectrometry (HPLC-(HR)MS and HPLC-MS-MS) were developed and established for analysis of these compounds in wastewater and to assess their effect on the environment. The methods developed enabled quantification at trace concentrations (limit of quantification (LOQ): 5 ng L(-1)). Of the steroids and stimulants under investigation, testosterone, methyltestosterone, and boldenone or ephedrine, amphetamine, and MDMA (3,4-methylendioxy-N-methylamphetamine) were observed at up to 5 microg L(-1) (ephedrine). Of the beta(2)-agonists salbutamol only, and of the diuretics furosemide and hydrochlorothiazide were confirmed in the extracts. Quite high concentrations of the PDE type V inhibitors sildenafil, tadalafil, and vardenafil and their metabolites were confirmed in fitness centre discharges (sildenafil: 1,945 ng L(-1)) whereas their concentrations in municipal wastewater did not exceed 35 ng L(-1). This study identified anabolic and doping drugs in wastewater for the first time. Results obtained from wastewater treatment plant effluents proved that these "dual-use-drugs", with the exception of hydrochlorothiazide, were mostly eliminated.

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A reliable and easy to use liquid chromatography/tandem mass spectrometry (LC/MS/MS) method was developed for the simultaneous quantification of urinary concentrations of cyclophosphamide (CP) and its main metabolites excreted in urine, i.e. N-dechloroethylcyclophosphamide (DCL-CP), 4-ketocyclophosphamide (4KetoCP), and carboxyphosphamide (CarboxyCP). Sample preparation consisted of dilution of urine with an aqueous solution of the internal standard D 4 -CP and methanol, and centrifugation. LC/MS/MS detection was performed using a triple-quadrupole mass spectrometer working in selected reaction monitoring mode. All analytes were quantified in a single run within 11.5 min. The limits of detection were 5 ng/mL for CP and 4KetoCP, 1 ng/mL for DCL-CP, and 30 ng/mL for CarboxyCP. Quantification ranges were adjusted to the expected concentrations in 24-h urine collections of patients treated with a polychemotherapy regimen (3-175 mg/mL for CP, 0.5-27 mg/mL for 4KetoCP and 0.17-9 mg/mL for CarboxyCP and DCL-CP, respectively). The N-lost derivative cyclophosphamide (CP) is widely used as an antineoplastic drug and is included in many polychemotherapy regimens. CP is a prodrug and requires oxidative biotransformation to evolve its cytotoxic activity. It is subject to a pronounced metabolism in the human body, leading to active and inactive metabolites. A hydroxylation in ring position 4 represents the activating step in CP metabolism. The product 4-hydroxycyclophosphamide (4-OHCP) is in equilibrium with its ring-opened tautomer aldophosphamide (AldoCP). In humans, this first step is mediated predominantly by the cytochrome P450 2B6 (CYP2B6) enzyme, and also by members of the CYP2C subfamily and CYP3A4. [1][2][3][4] Most of the intermediate product AldoCP is subject to a spontaneous, non-enzymatic b-elimination to release the active alkylating species phosphoramide mustard and the urotoxic acrolein. Apart from the renal elimination of unchanged drug, partially competitive steps occur leading to inactive metabolites. A fraction of the parent compound is inactivated to N-dechloroethylcyclophosphamide (DCL-CP) by sidechain oxidation mediated by CYP3A4.3,5 In turn, 4-OHCP and AldoCP are detoxified by oxidation to carboxyphosphamide (CarboxyCP) and 4-ketocyclophosphamide (4KetoCP), which are excreted in urine.During the last 25 years, several methods for the determination of CP and its metabolites have been described.6-10 Gas chromatography represents a very sensitive method for the detection of the parent compound, 9,10 DCL-CP 5 and 4KetoCP in biological fluids. In addition, HPLC methods for the determination of CP concentrations in vivo have also been used. 11,12 However, these methods are not very selective or sensitive because of the low wavelength necessary for UV detection (200 nm), and they include complex extraction procedures. 6,[13][14][15] For the more reactive compounds, assays are available which require a complex derivatization before quantification in order to stabilize the analytes. 16 -18 During the last few y...

The degradation products of the macrolide antibiotic erythromycin A (ERY) arising from direct ozone attack and hydroxyl radical attack are presented for the first time. Ozone treatment was carried out by spiking ozone stock solutions to solutions containing ERY-ERY:O 3 5 1:5 and 1:10 (M:M), while, in parallel, t-BuOH was used as a hydroxyl radical (NOH) scavenger. The advanced oxidation processes (AOPs) O 3 /UV, O 3 /H 2 O 2 , and UV/H 2 O 2 were carried out to recognize and verify possible differences between their primary degradation products; the initial concentrations were ERY:O 3 5 1:5 (M:M), ERY:O 3 :H 2 O 2 5 1:5:5 (M:M:M), or ERY:H 2 O 2 5 1:5 (M:M), respectively. Six degradation products were identified from ozonation-one originates from direct ozone attack on the tertiary amine group, while the others arise from radical ion attack, which might be formed during degradation of O 3 in water. Fewer primary degradation products were observed arising from NOH-based treatments (AOP) than from ozonation, possibly because the reaction of NOH radicals is non-selective and typically is diffusion-controlled. Four degradation products were detected by NOH radical attacks; two of them already were observed during ozonation, with one as an oxidized ERY molecule and the other as a non-oxidized fragment of the ERY molecule. Water Environ. Res., 82, 797 (2010).

Pharmaceutical residues in wastewater pose a challenge to wastewater treatment technologies. Constructed wetlands (CWs) are common wastewater treatment systems in rural areas and they discharge often in small water courses in which the ecology can be adversely affected by the discharged pharmaceuticals. Hence, there is a need for studies aiming to improve the removal of pharmaceuticals in CWs. In this study, the performance of a full-scale aerated sub-surface flow hybrid CW treating wastewater from a healthcare facility was studied in terms of common water parameters and pharmaceutical removal. In addition, a preliminary aquatic risk assessment based on hazard quotients was performed to estimate the likelihood of adverse effects on aquatic organisms in the forest creek where this CW discharges. The (combined) effect of aeration and hydraulic retention time (HRT) was evaluated in a laboratory-scale batch experiment. Excellent removal of the targeted pharmaceuticals was obtained in the full-scale CW (>90%) and, as a result, the aquatic risk was estimated low. The removal efficiency of only a few of the targeted pharmaceuticals was found to be dependent on the applied aeration (namely gabapentin, metformin and sotalol). Longer and the HRT increased the removal of carbamazepine, diclofenac and tramadol.