A case study to identify priority cytostatic contaminants in hospital effluents.

This study analyses the presence of 17 cytostatic agents from seven different groups, based on their different mechanisms of action, in the effluent from a medium-sized hospital located in eastern Spain. Analysis of the compounds found in the effluents studied involved solidphase extraction (SPE) coupled on-line to a high performance liquid chromatograph tandem mass spectrometer (HPLC-MS/MS). The environmental risk of the compounds studied was then assessed by calculating the hazard quotient (HQ), combining the measured environmental concentrations (MECs) with dose-response data based on the predicted no effect concentrations (PNECs). In addition, the environmental hazard associated was evaluated in accordance with their intrinsic characteristics by calculating the PBT (Persistence Bioaccumulation Toxicity) index. The results of this study showed the presence of seven of the 17 compounds analysed in a range of between 25 and 4761 ng/L. The highest concentrations corresponded to ifosfamide (58-4761 ng/L), methotrexate (394-4756 ng/L) and cyclophosphamide (46-3000 ng/L). Assessment of the environmental hazard showed that the three hormonal agents (tamoxifen and its metabolites endoxifen and hydroxytamoxifen) exhibited a maximum PBT value of 9 due to their inherent harm to the environment resulting from their characteristics of persistence, bioaccumulation and toxicity. A combined evaluation of the risk and environmental hazard showed that three of the 17 compounds studied, namely, ifosfamide, imatinib and irinotecan, all of which exhibited HQ values higher than 10 and PBT indices of 6, indicative of a particularly high potential to harm the environment, deserve special attention.

Ozonation of hospital raw wastewaters for cytostatic compounds removal. Kinetic modelling and economic assessment of the process.

The kinetics of the ozone consumption for the pretreatment of hospital wastewater has been analysed in order to determine the reaction rate coefficients between the ozone and the readily oxidisabled organic matter and cytostatic compounds. The wastewater from a medium size hospital was treated with ozone and peroxone methodologies, varying the ozone concentration, the reaction time and the hydrogen peroxide doses. The analysis shows that there are four cytostatic compounds, i.e. irinotecan, ifosfamide, cyclophosphamide and capecitabine, detected in the wastewaters and they are completely removed with reasonably short times after the ozone treatment. Considering the reactor geometry, the gas hydrodynamics, the mass transfer of ozone from gas to liquid and the reaction of all oxidisable compounds of the wastewater it is possible to determine the chemical ozone demand, COzD, of the sample as 256mgO3L(-1) and the kinetic rate coefficient with the dissolved organic matter as 8.4M(-1)s(-1). The kinetic rate coefficient between the ozone and the cyclophosphamide is in the order of 34.7M(-1)s(-1) and higher for the other cytostatics. The direct economic cost of the treatment was evaluated considering this reaction kinetics and it is below 0.3€/m(3) under given circumstances.

Drugs of abuse, cytostatic drugs and iodinated contrast media in tap water from the Madrid region (central Spain):A case study to analyse their occurrence and human health risk characterization.

This work analyses the presence of forty-eight emerging pollutants, including twenty-five drugs of abuse and metabolites, seventeen cytostatic drugs and six iodinated contrast media, in tap water from the Madrid Region. Analysis of the target compounds in the tap water was performed by means of (on-line or off-line) solid-phase extraction followed by analysis by liquid chromatography-tandem mass spectrometry. A preliminary human health risk characterization was undertaken for each individual compound and for different groups of compounds with a common mechanism of action found in tap water. The results of the study showed the presence of eight out of the twenty-five drugs of abuse and metabolites analysed, namely, the cocainics cocaine and benzoylecgonine, the amphetamine-type stimulants ephedrine, 3,4-methylenedioxymethamphetamine and methamphetamine, the opioid methadone and its metabolite 2-ethylene-1,5-dimethyl-3,3-diphenylpyrrolidine and, finally caffeine at concentrations ranging from 0.11 to 502 ng L(-1). Four out of the six analysed iodinated contrast media, namely, diatrizoate, iohexol, iomeprol and iopromide, were detected in at least one sample, with concentration values varying between 0.4 and 5 ng L(-1). Cytostatic compounds were not detected in any sample. Caffeine was the substance showing the highest concentrations, up to 502 ng L(-1), mainly in the drinking water sampling point located in Madrid city. Among the other drugs of abuse, the most abundant compounds were cocaine and benzoylecgonine, detected at concentrations ranging from 0.11 to 86 ng L(-1) and from 0.11 to 53 ng L(-1), respectively. Regarding iodinated contrast media, iohexol was the most ubiquitous and abundant compound, with a frequency of detection of 100% and concentrations from 0.5 to 5.0 ng L(-1) in basically the same range in all sampling points. Taking into account the results and types of treatment applied, ozonisation plus granular activated carbon filtration appears to be efficient in the removal of cocaine and benzoylecgonine. For the amphetamine-type stimulants, opioids and caffeine, ozonisation plus granular activated carbon filtration and ultrafiltration plus reverse osmosis showed higher removal efficiency than sand filtration. The human health risk characterization performed indicates that the lifetime consumption of the tap waters analysed has associated a negligible human health concern.

Assessment of benzophenone-4 reactivity with free chlorine by liquid chromatography quadrupole time-of-flight mass spectrometry.

The stability of the UV filter benzophenone-4 (BP-4) in free chlorine-containing water was investigated, for the first time, by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QqTOF-MS). High mass accuracy and resolution capabilities of this hybrid mass spectrometer were used for the reliable assignation of empirical formulae and chemical structures of BP-4 derivatives. Time-course profiles of the parent compound and its by-products were simultaneously recorded by direct injection of sample aliquots, after quenching the excess of chlorine, in the LC-QqTOF-MS system. At neutral pHs, in excess of chlorine, BP-4 showed a limited stability fitting a pseudo-first-order degradation kinetics. A noticeable reduction in the half-lives of BP-4 was observed when increasing the sample pH between 6 and 8 units and also in presence of bromide traces. The reaction pathway of this UV filter involved a first electrophilic substitution of hydrogen per chlorine (or bromide) in the phenolic ring, followed by oxidation of the carbonyl moiety to an ester group, which induced a further electrophilic substitution in the same aromatic ring. Above reactions were also noticed when mixing a BP-4 containing personal care product with chlorinated tap water and in chlorinated swimming pool and sewage water, previously spiked with a BP-4 standard.

Silicone discs as disposable enrichment probes for gas chromatography-mass spectrometry determination of UV filters in water samples.

This work describes an effective, low solvent consumption and affordable sample preparation approach for the determination of eight UV filters in surface and wastewater samples. It involves sorptive extraction of target analytes in a disposable, technical grade silicone disc (5 mm diameter × 0.6 mm thickness) followed by organic solvent desorption, large volume injection (LVI), and gas chromatography-mass spectrometry determination. Final working conditions involved overnight extraction of 100-mL samples, containing 10% of methanol, followed by analytes desorption with 0.2 mL of ethyl acetate. The method provides linear responses between the limits of quantification (from 0.003 to 0.040 ng mL(-1)) and 10 ng mL(-1), an intra-day precision below 13%, and low matrix effects for surface, swimming pool, and treated sewage water samples. Moreover, the extraction yields provided by silicone discs were in excellent agreement with those achieved using polydimethylsiloxane-covered stir bars. Several UV filters were found in surface and sewage water samples, with the maximum concentrations corresponding to octocrylene.

Optimization of pressurized liquid extraction and purification conditions for gas chromatography-mass spectrometry determination of UV filters in sludge.

This work presents an effective sample preparation method for the determination of eight UV filter compounds, belonging to different chemical classes, in freeze-dried sludge samples. Pressurized liquid extraction (PLE) and gas chromatography-mass spectrometry (GC-MS) were selected as extraction and determination techniques, respectively. Normal-phase, reversed-phase and anionic exchange materials were tested as clean-up sorbents to reduce the complexity of raw PLE extracts. Under final working conditions, graphitized carbon (0.5 g) was used as in-cell purification sorbent for the retention of co-extracted pigments. Thereafter, a solid-phase extraction cartridge, containing 0.5 g of primary secondary amine (PSA) bonded silica, was employed for off-line removal of other interferences, mainly fatty acids, overlapping the chromatographic peaks of some UV filters. Extractions were performed with a n-hexane:dichloromethane (80:20, v:v) solution at 75°C, using a single extraction cycle of 5 min at 1500 psi. Flush volume and purge time were set at 100% and 2 min, respectively. Considering 0.5 g of sample and 1 mL as the final volume of the purified extract, the developed method provided recoveries between 73% and 112%, with limits of quantification (LOQs) from 17 to 61 ng g(-1) and a linear response range up to 10 µg g(-1). Total solvent consumption remained around 30 mL per sample. The analysis of non-spiked samples confirmed the sorption of significant amounts of several UV filters in sludge with average concentrations above 0.6 µg g(-1) for 3-(4-methylbenzylidene) camphor (4-MBC), 2-ethylhexyl-p-methoxycinnamate (EHMC) and octocrylene (OC).

Solid-phase microextraction followed by gas chromatography-mass spectrometry for the determination of ink photo-initiators in packed milk.

A novel, single step method for the determination of seven ink photo-initiators in carton packed milk samples is described. Solid-phase microextraction (SPME) and gas chromatography (GC), combined with mass spectrometry (MS), were used as sample preparation and determination techniques, respectively. Parameters affecting the performance of the microextraction process were thoroughly evaluated using uni- and multivariate optimization strategies, based on the use of experimental factorial designs. The coating of the SPME fibre, together with the sampling mode and the temperature were the factors playing a major influence on the efficiency of the extraction. Under final conditions, 1.5 mL of milk and 8.5 mL of ultrapure water were poured in a glass vessel, which was closed and immersed in a water boiling bath. A poly(dimethylsiloxane)-divinylbenzene (PDMS-DVB) coated fibre was exposed directly to the diluted sample for 40 min. After that, the fibre was desorbed in the injector of the GC-MS system for 3 min. The optimized method provided limits of quantification (LOQs) between 0.2 and 1 microg L(-1) and a good linearity in the range between 1 and 250 microg L(-1). The inter-day precision remained below 15% for all compounds in spiked whole milk. The efficiency of the extraction changed for whole, semi-skimmed and skimmed milk; however, no differences were noticed among the relative recoveries achieved for milk samples, from different brands, with the same fat content.

Dispersive liquid-liquid microextraction followed by gas chromatography-mass spectrometry for the rapid and sensitive determination of UV filters in environmental water samples.

The performance of the dispersive liquid-liquid microextraction (DLLME) technique for the determination of eight UV filters and a structurally related personal care species, benzyl salicylate (BzS), in environmental water samples is evaluated. After extraction, analytes were determined by gas chromatography combined with mass spectrometry detection (GC-MS). Parameters potentially affecting the performance of the sample preparation method (sample pH, ionic strength, type and volume of dispersant and extractant solvents) were systematically investigated using both multi- and univariant optimization strategies. Under final working conditions, analytes were extracted from 10 mL water samples by addition of 1 mL of acetone (dispersant) containing 60 µL of chlorobenzene (extractant), without modifying either the pH or the ionic strength of the sample. Limits of quantification (LOQs) between 2 and 14 ng L(-1), inter-day variability (evaluated with relative standard deviations, RSDs) from 9% to 14% and good linearity up to concentrations of 10,000 ng L(-1) were obtained. Moreover, the efficiency of the extraction was scarcely affected by the type of water sample. With the only exception of 2-ethylhexyl-p-dimethylaminobenzoate (EHPABA), compounds were found in environmental water samples at concentrations between 6 ± 1 ng L(-1) and 26 ± 2 ng mL(-1).

Solid-phase extraction followed by liquid chromatography-tandem mass spectrometry for the determination of hydroxylated benzophenone UV absorbers in environmental water samples.

A procedure for the determination of six derivatives of 2-hydroxybenzophenone, used as UV absorbers, in water samples is presented. Compounds were first concentrated using a solid-phase extraction (SPE) cartridge and then selectively determined by liquid chromatography-tandem mass spectrometry (LC-MS/MS) using electrospray ionization (ESI). The effect of different parameters on the performance of concentration and determination steps is discussed. The highly polar and acidic 2-hydroxy-4-methoxybenzophenone-5-sulfonic acid (BP-4) required the use of ammonium acetate as modifier during desorption of SPE cartridges and also to improve the performance of its separation in the LC column. Under optimized conditions, the proposed method provided limits of quantification from less than 1 to 32ngL(-1), depending on the compound and the type of water sample. Recoveries from the SPE step (83-105%) remained unaffected by the nature of the matrix; however, the efficiency of electrospray ionization was compound and sample dependant. Real sample analysis reflected the presence of three of the six investigated species (BP-4, 2-hydroxy-4-methoxybenzophenone, BP-3, and 2,4-dihydroxybenzophenone, BP-1) in the aquatic environment, particularly in raw wastewater samples. In this latter matrix, BP-4 was the compound presenting the highest concentrations; moreover, it was poorly removed in sewage treatment plants and consequently it also appeared in river water.

Determination of selected UV filters in indoor dust by matrix solid-phase dispersion and gas chromatography-tandem mass spectrometry.

A simple, inexpensive sample preparation procedure, based on the matrix solid-phase dispersion (MSPD) technique, for the determination of six UV filters: 2-ethylhexyl salicylate (EHS), 3,3,5-trimethylcyclohexyl salicylate (Homosalate, HMS), 3-(4-methylbenzylidene) camphor (4-MBC), isoamyl-p-methoxycinnamate (IAMC), 2-ethylhexyl-p-methoxycinnamate (EHMC) and octocrylene (OCR), in dust from indoor environments is presented and the influence of several operational parameters on the extraction performance discussed. Under the final working conditions, sieved samples (0.5 g) were mixed with the same amount of anhydrous sodium sulphate and dispersed with 2 g of octadecyl bonded silica (C18) in a mortar with a pestle. This blend was transferred to a polypropylene solid-phase extraction cartridge containing 2 g of activated silica, as the clean-up co-sorbent. The cartridge was first rinsed with 5 mL of n-hexane and the analytes were then recovered with 4 mL of acetonitrile. This extract was adjusted to 1 mL, filtered and the compounds were determined by gas chromatography combined with tandem mass spectrometry (GC-MS/MS). Recoveries for samples spiked at two different concentrations ranged between 77% and 99%, and the limits of quantification (LOQs) of the method between 10 and 40 ng g(-1). Analysis of settled dust from different indoor areas, including private flats, public buildings and vehicle cabins, showed that EHMC and OCR were ubiquitous in this matrix, with maximum concentrations of 15 and 41 microg g(-1), respectively. Both UV filters were also quantified in dust reference material SRM 2585 for first time. EHS, 4-MBC and IAMC were detected in some of the analyzed samples, although at lower concentrations than EHMC and OCR.

Sensitive determination of salicylate and benzophenone type UV filters in water samples using solid-phase microextraction, derivatization and gas chromatography tandem mass spectrometry.

A sensitive procedure for the determination of three UV filters: ethylhexyl salicylate (EHS), 3,3,5-trimethylcyclohexyl salicylate (Homosalate, HMS), 2-hydroxy-4-methoxybenzophenone (BP-3) and two related hydroxylated benzophenones (2,4-dihydroxybenzophenone, BP-1 and 2,2'-dihydroxy-4-methoxybenzophenone, BP-8) in water samples is presented. Analytes were first concentrated on the coating of a solid-phase microextraction (SPME) fibre, on-fibre silylated and then determined using gas chromatography combined with tandem mass spectrometry (GC-MS/MS). Factors affecting the performance of extraction and derivatization steps are thoroughly evaluated and their effects on the yield of the sample preparation discussed. Under final working conditions, a PDMS-DVB coated SPME fibre was exposed directly to 10 mL of water, adjusted at pH 3, for 30 min. After that, the fibre was placed in the headspace (HS) of a 1.5 mL vial containing 20 microL of N-methyl-N-(trimethylsilyl)-trifluoroacetamide (MSTFA). On-fibre silylation of hydroxyl groups contained in the structure of target compounds was performed at 45 degrees C for 10 min. The whole sample preparation process was completed in 40 min, providing limits of quantification from 0.5 to 10 ng L(-1) and acceptable precision (RSDs under 13%) for samples spiked at different concentrations. All compounds could be accurately determined in river and treated wastewater (relative recoveries from 89 to 115%) using standards in ultrapure water, whereas standard addition is recommended to quantify their levels in untreated wastewater. Analysis of wastewater revealed the systematic presence of BP-3 and BP-1 in raw samples with maximum concentrations close to 500 and 250 ng L(-1), respectively.

Study of some UV filters stability in chlorinated water and identification of halogenated by-products by gas chromatography-mass spectrometry.

This work studies the stability of three UV filters: 2-ethylhexyl salicylate (ES), 2-ethylhexyl 4-(dimethylamino) benzoate (EHPABA) and 2-hydroxy-4-methoxybenzophenone (BP-3), in water samples containing low concentrations of free chlorine. Moreover, 2,4-dihydroxybenzophenone (2,4-DHBP), a metabolite of BP-3, was also included in some of the performed assays. Experiments were carried out considering free chlorine and analytes concentrations at the microg mL(-1) and ng mL(-1) level, respectively. Gas chromatography with mass spectrometry was used to follow the time course of target compounds and to identify their halogenated by-products. Concentration of water samples with solid-phase extraction cartridges and derivatization (silylation) of some species were also employed to improve their detectability. Under the experimental conditions explored in this work, ES showed an acceptable stability whereas the rest of species reacted with free chlorine at significant rates following pseudo-first-order kinetics. Their half-lives ranged from 0.4 to 25 min depending on the UV filter, chlorine concentration, water pH and presence of bromide traces. For EHPABA a relatively simple degradation pathway was established. It consisted of aromatic substitution of one atom of hydrogen per chlorine or bromide. The same reaction pattern was observed for BP-3 leading, in this case, to mono- and di-halogenated by-products. In addition, several halogenated forms of 3-methoxyphenol were identified as BP-3 cleavage by-products.

Formation of halogenated by-products of parabens in chlorinated water.

Chemical transformations of four alkyl esters of p-hydroxybenzoic acid, parabens, in chlorinated water samples are investigated. Quantification of the parent species and identification of their reaction by-products were performed using gas chromatography in combination with mass spectrometry. Experiments were accomplished considering free chlorine and paraben concentrations at the mg L(-1) and microg L(-1) level, respectively. Concentration of water samples, using solid-phase extraction, and silylation of the target species were carried out in order to improve the detectability of parent species and their possible transformation products, achieving quantification limits at the low ng L(-1) level. Under employed experimental conditions, the decrease in the concentrations of parabens followed pseudo-first-order kinetics. Half-lives values obtained for model ultrapure water solutions were in good agreement with those observed in tap water samples. For the first type of sample, only two by-products were detected for each paraben. They corresponded to chlorination of the aromatic ring in one or two carbons situated in ortho-positions to the hydroxyl group. Both species were also generated after the addition of parabens to chlorinated tap water. Moreover, three new transformation products were noticed for each parent compound. They were identified as bromo- and bromochloro-parabens, formed due to the existence of traces of bromide in tap water sources. Experiments carried out by mixing paraben-containing personal care products with tap water, containing free chlorine, confirmed the formation of all above described halogenated by-products. In addition, the presence of the di-chlorinated forms of methyl and propyl paraben has been detected for first time in raw sewage water samples.