Determination of some acidic drugs in surface and sewage treatment plant waters by capillary electrophoresis-electrospray ionization-mass spectrometry

We describe an analytical method involving solid-phase extraction (SPE) and capillary zone electrophoresis-electrospray ionization-mass spectrometry (CZE-ESI-MS) for determining some pharmaceutical compounds - naproxen, clofibric acid and bezafibrate - in real water samples. The electrospray parameters were optimized to maximize sensitivity. When a mixed aqueous-organic solvent and CZE-ESI-MS were used to analyze these drugs in water samples, the capillary was coated with hexadimethrin bromide (HDB) to permanently reverse the EOF. The method was developed from off-line SPE-CZE-MS and was validated with surface water. The detection limits were 100 ng.L(-1) for all analytes. The method was applied to analyze water samples from the influent and effluent of a sewage treatment plant. A liquid-liquid extraction step was required before SPE, and the compounds studied were found, some of them between detection and quantification limits.     

An LC-MS method for the determination of pharmaceutical compounds in wastewater treatment plant influent and effluent samples

Pharmaceuticals are continually introduced into the environment as a result of industrial and domestic use. In recent years they have emerged as environmental pollutants. An analytical method has been developed allowing for simultaneous detection and identification of 20 pharmaceutical compounds from various therapeutic classes using solid phase extraction (SPE) followed by liquid chromatography-electrospray ionisation mass spectrometry (LC-MS/MS). The limits of detection and limits of quantitation for the method were in the ng/L-microg/L range. The method was applied to influent and effluent samples from three wastewater treatment plants (WWTPs). Fifteen compounds were identified in the sample matrix with salicylic acid and ibuprofen being the most abundant at 9.17 and 3.20 microg/L respectively.     

Simultaneous determination of macrolides, sulfonamides, and other pharmaceuticals in water samples by solid-phase extraction and LC-(ESI) MS

This paper describes a method for determining 11 pharmaceuticals in various water sources by SPE followed by LC-(ESI) MS. SPE was carried out with Oasis HLB and the recoveries were 33-67% for 250 and 100 mL sewage water, 55-77% for 500 mL river water and 72-98% for 1 L tap water, with the exception of sulfamethoxazole and omeprazole which showed lower recoveries in all kinds of sample. The LODs in river water were of 5 ng/L for sulfadiazine, trimethoprim, sulfamethazine, sulfamethoxazole, and ranitidine and 10 ng/L for the other compounds. The highest concentrations found in river waters were for sulfamethoxazole (50 ng/L). In influent sewage waters, ranitidine was the most commonly detected compound with a maximum value of 0.24 microg/L.     

固相微萃取与色谱联用方法分析水中12种有机氯化合物

运用顶空固相微萃取与色谱闻用方法（ＨＳ－ＳＰＭＥ－ＧＣ）对水中的残留有机氯化合物进行了分析。对影响ＨＳ－ＳＰＭＥ－ＧＣ分析灵敏度的各种实验因素如涂层种类,萃取温度、平衡时间,离子浓度等进行了讨论并将该方法与固相萃取法（ＳＰＥ）,液液萃取法（ＬＬＥ）作了对比,同时考察了常见环境共存污染物直链烷基苯磺酸钠（ＬＡＳ）对几种方法的影响。     

Simultaneous analysis of 16 sulfonamide and trimethoprim antibiotics in environmental waters by liquid chromatography-electrospray tandem mass spectrometry

A sensitive liquid chromatography-electrospray tandem mass spectrometry method combined with solid-phase extraction and silica cartridge cleanup was established for 16 sulfonamides and trimethoprim in various water matrices. Signal suppression of all target analytes in sewage treatment plant influent, effluent and river water was improved by this method developed in this study. The method detection limits for 17 analytes were 20-200 pg/L for influent, 16-120 pg/L for effluent and 8.0-60 pg/L for river water with overall mean recoveries of 62-102% in all studied matrices. This method was used to analyze residual sulfonamides and trimethoprim in wastewater and river samples from Japan, and 8 analytes (0.08 (sulfadimethoxine)-161 ng/L (sulfapyridine) in wastewater and 10 (0.03 (sulfamethizol)-8.9 ng/L (sulfaquinoxaline) in river samples were detected.     

On-line solid phase extraction LC-MS/MS analysis of pharmaceutical indicators in water: A green alternative to conventional methods

A method using automated on-line solid phase extraction (SPE) directly coupled to liquid chromatography/tandem mass spectrometry (LC-MS/MS) has been developed for the analysis of six pharmaceuticals by isotope dilution. These selected pharmaceuticals were chosen as representative indicator compounds and were used to evaluate the performance of the on-line SPE method in four distinct water matrices. Method reporting limits (MRLs) ranged from 10 to 25 ng/L, based on a 1 mL extraction volume. Matrix spike recoveries ranged from 88 to 118% for all matrices investigated, including finished drinking water, surface water, wastewater effluent and septic tank influent. Precision tests were performed at 50 and 1000 ng/L with relative standard deviations (RSDs) between 1.3 and 5.7%. A variety of samples were also extracted using a traditional off-line automated SPE method for comparison. Results for both extraction methods were in good agreement; however, on-line SPE used approximately 98% less solvent and less time. On-line SPE coupled to LC-MS/MS analysis for selected indicators offers an alternative, more environmentally friendly, method for pharmaceutical analysis in water by saving time and costs while reducing hazardous waste and potential environmental pollution as compared with off-line SPE methods.     

Multiresidue method for the analysis of emerging contaminants in wastewater by ultra performance liquid chromatography-time-of-flight mass spectrometry

A multiresidue method for screening of emerging contaminants in aquatic environments was developed. The method was based on sample pretreatment with solid phase extraction (SPE) and analysis with an ultra performance liquid chromatograph-time-of-flight mass spectrometer (UPLC-TOF-MS). The method was optimized and tested with standard solutions of model compounds containing 84 pesticides and pharmaceuticals. Four different SPE sorbents were evaluated to gain maximum recovery for the analytes. For the final procedure a combination of two different sorbents was chosen. In spite of high matrix suppression, the method quantification limits (MQLs) were acceptable. Therefore, the method can be used for screening known target compounds. The applicability of the method for posttarget and nontarget screening will be reported later. To preliminarily assess the quantitative performance of the method, some compounds in wastewater effluent were quantified using the standard addition method. Three pesticides and eight pharmaceuticals were found in concentrations up to ～2200 ng/L.     

Trace-level determination of pharmaceutical residues by LC-MS/MS in natural and treated waters. A pilot-survey study

A pilot-survey study was performed by collecting samples (influent and effluent wastewaters, rivers and tap waters) from different locations in Europe (Spain, Belgium, Germany and Slovenia). A solid-phase extraction (SPE) followed by liquid chromatography–tandem mass spectrometry method was applied for the determination of pharmaceuticals (ibuprofen, naproxen, ketoprofen, diclofenac and clofibric acid). Method detection limits and method quantification limits were at the parts-per-trillion level (7.5–75 ng/L). The recovery rates of the SPE from deionized water and effluent wastewater samples spiked at 100- and 1,000-ng/L levels ranged from 87 to 95%. Identification criteria in compliance with the EU regulation for confirmatory methods of organic residues were applied. A detailed study of signal suppression evaluation for analysis of pharmaceutical residues in effluent wastewaters is presented.     

Analysis of neutral and basic pharmaceuticals in sewage treatment plants and in recipient rivers using solid phase extraction and liquid chromatography-tandem mass spectrometry detection

Analytical method was developed which allowed for the detection of four beta blockers (acebutolol, atenolol, metoprolol and sotalol), an antiepileptic drug (carbamazepine) and three fluoroquinolone antibiotics (ciprofloxacin, ofloxacin and norfloxacin) with a single pre-treatment and chromatographic method. The method included an isolation and concentration procedure using solid phase extraction, a separation step using high performance liquid chromatography and a detection procedure applying triple quadrupole mass spectrometry, which was working in the multiple reaction monitoring mode. The method was validated for ground, surface and sewage influent and effluent waters. Due to ion suppression in the electrospray source, the signals monitored for the analytes were less intense in sewage waters compared to ground and surface waters. The limits of quantification were as low as 1 ng L(-1) in ground water and 3.5 ng L(-1) in sewage influent. The method was successfully applied to the determination of the target compounds in raw and treated sewages of three treatment plants in Finland and in their recipient rivers. The results showed that many of the studied compounds pose a moderate to high persistency in sewage treatment as well as in the recipient rivers. The analytical protocol presented may be used for more in-depth studies on the occurrence and fate of these commonly used pharmaceuticals in the sewage treatment plants and in the aquatic environment.     

Analysis of linear alkylbenzene sulfonate homologues in environmental water samples by mixed admicelle-based extraction and liquid chromatography/mass spectrometry

Hemimicelles and admicelles of cetyltrimethylammonium bromide (CTAB) and cetylpyridinium chloride (CPC), adsorbed onto silica, were tested as sorbents for the solid phase extraction (SPE) of linear alkylbenzene sulfonate (LAS) homologues from environmental water samples. LASs were quantitatively retained on both surfactants due to high hydrophobic and ionic interactions, which led to the formation of analyte-extractant mixed aggregates. Parameters affecting the SPE of LASs were optimised. Recoveries of analytes from wastewater influent and effluent and river water samples ranged between 86 and 110%. Combination of SPE with liquid chromatography/mass spectrometry provided detection limits for the different LAS homologues of about 4 ng L(-1). The precision of the method, expressed as relative standard deviation, ranged from 5 to 9%. The method was applied to the analysis of LASs in wastewater and river samples using sample volumes between 10 and 25 mL. The LAS concentrations found ranged from 9 to 503 microg L(-1). No cleaning step was required to get accurate results.     

Determination of pharmaceuticals from different therapeutic classes in wastewaters by liquid chromatography–electrospray ionization–tandem mass spectrometry

A sensitive analytical method has been developed and validated for simultaneous determination of pharmaceuticals from different therapeutic classes, i.e. five sulfonamide (SA) and trimethoprim antimicrobials and the anti-inflammatory drug diclofenac, in effluent wastewaters at trace levels. Effluent samples from treatment of wastewater were enriched by solid-phase extraction (SPE) using the Waters Oasis HLB cartridge. The analytes were identified and quantified by reversed-phase liquid chromatography-tandem mass spectrometry operated in the selected reaction monitoring (SRM) mode, using positive electrospray ionization. The pharmaceuticals were, consequently, quantified both by use of isotopically labelled internal standards and by standard addition methods to address the issue of matrix effects related to signal suppression by co-eluting compounds. Average recoveries from fortified samples were usually >70%, with relative standard deviations below 20%. Method detection limits in wastewater matrices were between 7.0 and 10 ng L(-1). Identification points (IPs) were used for unequivocal identification of target analytes in real samples. Diclofenac, trimethoprim, and sulfamethoxazole were mainly detected, in the concentration range 10 to 400 ng L(-1), in effluent samples collected from four different sewage-treatment plants in Greece.     

Pharmaceutical determination in surface and wastewaters using high-performance liquid chromatography-(electrospray)-mass spectrometry

A method was developed to determine 11 pharmaceutical compounds in water samples. The method uses SPE and HPLC coupled to MS (LC/MS) using ESI in both positive and negative modes. Three different sorbents were compared for the extraction of analytes from river and sewage treatment plant (STP) waters and OASIS HLB provided the best results. For the solid-phase extraction of 500 mL of river water samples, the recoveries were between 41 and 101% with the exception of acetaminophen, salicylic acid and naproxen. The LODs were between 3 and 5 ng/L for all the compounds, except naproxen which had an LOD of 15 ng/L. Acetaminophen, caffeine, carbamazepine, bezafibrate and ibuprofen were found in three of the tested river samples at ng/L levels and among them, the highest values were for caffeine and bezafibrate with 305 and 363 ng/L, respectively. For the influent and effluent water samples of the STP, volumes of 100 and 250 mL were used, respectively, to obtain acceptable recoveries. All the compounds showed recoveries between 33 and 91% for effluent samples and 33-72% for influent samples, with the exception of acetaminophen, salicylic acid and bezafibrate, which had lower recoveries. The method developed enabled pharmaceuticals in the influent and effluent sewage waters to be determined in five campaigns carried out between February 2004 and June 2005. Several pharmaceuticals were found in the influent samples: for instance, maximum concentrations of ibuprofen and caffeine were 6 and 40 microg/L, respectively.     

Automated on-line in-tube solid-phase microextraction followed by liquid chromatography/electrospray ionization-mass spectrometry for the determination of chlorinated phenoxy acid herbicides in environmental waters

A method for the determination of six chlorinated phenoxy acid herbicides in river water was developed using in-tube solid-phase microextraction (SPME) followed by liquid chromatography/electrospray ionization-mass spectrometry (LC/ESI-MS). In-tube SPME is an extraction technique for organic compounds in aqueous samples, in which analytes are extracted from a sample directly into an open tubular capillary by repeated draw/eject cycles of the sample solution. Simple mass spectra with strong signals corresponding to [M-H]- and [M-RCOOH]- were observed for all herbicides tested in this study. The best separation of these compounds was obtained with a C18 column using linear gradient elution with a mobile phase of acetonitrile-water containing 5 mmol l-1 dibutylamine acetate (DBA). To optimize the extraction of herbicides, several in-tube SPME parameters were examined. The optimum extraction conditions were 25 draw/eject cycles of 30 microliters of sample in 0.2% formic acid (pH 2) at a flow rate of 200 microliters min-1 using a DB-WAX capillary. The herbicides extracted by the capillary were easily desorbed by 10 microliters acetonitrile. Using in-tube SPME-LC/ESI-MS with time-scheduled selected ion monitoring, the calibration curves of herbicides were linear in the range 0.05-50 ng ml-1 with correlation coefficients above 0.999. This method was successfully applied to the analysis of river water samples without interference peaks. The limit of quantification was in the range 0.02-0.06 ng ml-1 and the limit of detection (S/N = 3) was in the range 0.005-0.03 ng ml-1. The repeatability and reproducibility were in the range 2.5-4.1% and 6.2-9.1%, respectively.     

Multi-residue analysis of drugs of abuse in wastewater and surface water by solid-phase extraction and liquid chromatography-positive electrospray ionisation tandem mass spectrometry

A new-multi residue method was developed for the environmental monitoring of 65 stimulants, opiod and morphine derivatives, benzodiazepines, antidepressants, dissociative anaesthetics, drug precursors, human urine indicators and their metabolites in wastewater and surface water. The proposed analytical methodology offers rapid analysis for a large number of compounds, with low limits of quantification and utilises only one solid-phase extraction-ultra performance liquid chromatography-positive electrospray ionisation tandem mass spectrometry (SPE-LC-MS/MS) method, thus overcoming the drawbacks of previously published procedures. The method employed solid phase extraction with the usage of Oasis MCX sorbent and subsequent ultra performance liquid chromatography-positive electrospray ionisation tandem mass spectrometry. The usage of a 1.7 μm particle size column (1 mm×150 mm) resulted in very low flow rates (0.04 mLmin(-1)), and as a consequence gave good sensitivity, low mobile phase consumption and short retention times for all compounds (from 2.9 to 23.1 min). High SPE recoveries (>60%) were obtained for the majority of compounds. The mean correlation coefficients of the calibration curves were typically higher than 0.997 and showed good linearity in the range 0-1000 μgL(-1). The method limits of detection ranged from 0.1 ngL(-1) for compounds including cocaine, benzoylecgonine, norbenzoylecgonine and 2-oxo-3-hydroxy-LSD to 100 ngL(-1) for caffeine. Method quantification limits ranged from 0.5 to 154.2 ngL(-1). Intra- and inter-day repeatabilities were on average less than 10%. The method accuracy range was within -33.1 to 30.1%. The new multi-residue method was used to analyse drugs of abuse in wastewater and river water in the UK environment. Of the targeted 65 compounds, 46 analytes were detected at levels above the method quantification limit (MQL) in wastewater treatment plant (WWTP) influent, 43 in WWTP effluent and 36 compounds in river water.     

Determination of ofloxacin, norfloxacin, and ciprofloxacin in sewage by selective solid-phase extraction, liquid chromatography with fluorescence detection, and liquid chromatography--tandem mass spectrometry

A solid-phase extraction (SPE) and liquid chromatographic (LC) method was developed for the determination of selected fluoroquinolone (FQ) drugs including ofloxacin, norfloxacin, and ciprofloxacin in municipal wastewater samples. Extraction of the FQs was carried out with a weak cation exchanger SPE cartridge, the Oasis WCX. The cartridge was washed with water and methanol as a cleanup before the FQs were eluted by a mixture of methanol, acetonitrile, and formic acid. Separation of the FQs was achieved by using a Zorbax SB-C8 column under isocratic condition at a flow rate of 0.2mL/min. Recoveries of the FQs in spiked final effluent samples were between 87 and 94% with a relative standard deviation of less than 6%. Several techniques have been evaluated for the detection of FQs in sewage extracts; they included fluorescence detection and electrospray ionization (ESI) mass spectrometry using either mass-selective detection or tandem mass spectrometry (MS/MS). When they were applied to sewage influent and effluent samples, the LC-MS/MS technique operating in the multiple reaction monitoring (MRM) mode proved to be best suited for the determination of FQs in sewage samples as it provided the highest sensitivity (limit of quantification 5ng/L) and selectivity. The observation of signal suppression (matrix effect) for some FQs in ESI LC-MS and LC-MS/MS is discussed and a solution is proposed. The three FQs were detected in all the sewage samples tested in this work, with median concentrations between 34 and 251ng/L.     

Simultaneous determination of isoflavones and lignans at trace levels in natural waters and wastewater samples using liquid chromatography/electrospray ionization ion trap mass spectrometry

A high-performance liquid chromatography/electrospray ionization ion trap mass spectrometry (HPLC/ESI-MSn) method has been developed for the trace determination of phytoestrogens in aquatic environmental samples. The method includes solid-phase extraction (SPE) and analysis using liquid chromatography/electrospray ionization ion trap mass spectrometry. The aquatic environmental samples, influent of a wastewater treatment plant (WWTP) and creek water, were adjusted to pH approximately 5 before extraction. The analyzed phytoestrogens were identified by an MSn method and quantified against a deuterated internal standard (genistein-3',5',6,8-D4). In negative ion mode, 0.1% formic acid was employed in acetonitrile/water mobile phase. The method detection limits ranged from 0.5 to 10 ng/L in WWTP influent and from 0.1 to 5 ng/L in creek water. Average SPE recoveries for the analyzed phytoestrogens ranged from 85 to 95%, with a relative standard deviation (RSD) (%) ranging from 3.9 to 6.5. The concentrations of the six analyzed phytoestrogens varied from 0.2 to 600 ng/L with high levels of enterolignans (enterolactone and enterodiol) found in the collected wastewater. The method is shown to be suitable for the determination of phytoestrogens in aquatic environmental samples at nano- and sub-nanogram per liter levels.     

SPE/LC/ESI/MS with phthalic anhydride derivatisation for the determination of alcohol ethoxylate surfactants in sewage influent and effluent samples

A new method for the analysis of alcohol ethoxylates (AEs) using electrospray ionisation liquid chromatography/mass spectrometry (ESI LC/MS) is described. The procedure incorporates a novel derivatisation step with phthalic anhydride for the analysis of EO0-20 ethoxylates in a single analysis. The derivatives obtained have proved to be very stable and the negative ion spectra show reduced background ions and competing adduct formation as compared to positive ion spectra. An automated solid phase extraction (SPE) step is used to allow both pre-concentration and clean-up of the environmental samples. The method provides more efficient recovery of AEs across the C12-C18 range than previously reported in the literature. Recoveries from final effluent spiked at 100 microg/L total AE, for the 126 species analysed, were found to be in the range 55-117%, with approximately 100 of the individual analytes having recoveries of 90-105%. An LOD of 0.02 microg/L for individual ethoxylate components is reported with the instrument operated in scan mode over the range m/z 300-1300. The method was applied to sewage effluent and influent samples, with AEs determined at approximately 7 and 5000 microg/L, respectively.     

Analysis of terpenes in white wines using SPE-SPME-GC/MS approach

Terpenes contribute to some white wines aroma, especially these produced from Muscat grapes and others aromatic ones of high terpene contents (Gewürtztramminer, Traminer, Huxel, Sylvaner). Terpenes are present in wine in free and bound (in a form of glycosides) forms. Analyses of bound terpenes are usually performed using solid phase extraction after hydrolysis of glycosides. A new method for determination of terpenes from wine, focused on determination of terpenes released after acidic hydrolysis, based on solid phase extraction (SPE) followed by solid phase microextraction (SPME) was developed. Non-polar (free) and polar (bound terpenes) fractions were separated on 500 mg C18 cartridges. Bound terpenes were sampled using SPME immediately after acidic hydrolysis in non-equilibrium conditions. Application of combined SPE-SPME approach allowed quantification of selected terpenes in lower concentrations than in SPE approach and added a selectivity to the method, which enabled detection of compounds non-detectable in SPE extracts. Results obtained by SPE and SPE-SPME approach were correlated for free terpenes and those released after acid hydrolysis 20 white wines obtained from different grape varieties (R² = 0.923). Although developed for wine terpenes analysis, SPE followed by SPME approach has a great potential in analysis of other bound wine flavor compounds, especially those potent odorants present in trace amounts.     

固相萃取-大体积程序升温进样气相色谱-三重四极杆串联质谱测定饮用水中3种挥发性N-亚硝胺

建立了固相萃取大体积程序升温进样气相色谱-三重四极杆质谱联用（GC-QqQ-MS/MS）同时测定饮用水中N-亚硝基二甲胺、N-亚硝基甲基乙基胺及N-亚硝基二乙基胺的分析方法。用椰壳活性炭固相萃取小柱萃取水样中待测物组分，少量二氯甲烷洗脱、无水硫酸钠脱水，大体积程序升温进样，气相色谱-三重四极杆质谱联用仪进行多反应监测（MRM）模式检测，外标法定量。3种N-亚硝胺在1~50 ng/L范围内线性关系良好，相关系数（r²）均大于0.999，在饮用水中进行10、20和50 ng/L水平的添加，3种待测物平均加标回收率为94.8%~109%，相对标准偏差（RSD）为4.44%~8.10%（n=5），定量限（LOQ）为0.08~0.7 ng/L。该法灵敏、准确、简单、可靠，适用于饮用水中3种N-亚硝胺组分的痕量检测。     

Simultaneous ultra-high-pressure liquid chromatography–tandem mass spectrometry determination of amphetamine and amphetamine-like stimulants,cocaine and its metabolites,and a cannabis metabolite in surface water and urban wastewater

An ultra-high-pressure liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method has been developed for the simultaneous quantification and confirmation of 11 basic/acidic illicit drugs and relevant metabolites in surface and urban wastewater at ng/L levels. The sample pre-treatment consisted of a solid-phase extraction using Oasis MCX cartridges. Analyte deuterated compounds were used as surrogate internal standards (except for norbenzoylecgonine and norcocaine) to compensate for possible errors resulting from matrix effects and those associated to the sample preparation procedure. After SPE enrichment, the selected drugs were separated within 6 min under UHPLC optimized conditions. To efficiently combine UHPLC with MS/MS, a fast-acquisition triple quadrupole mass analyzer (TQD from Waters) in positive-ion mode (ESI+) was used. The excellent selectivity and sensitivity of the TQD analyzer in selected reaction monitoring mode allowed quantification and reliable identification at the LOQ levels. Satisfactory recoveries (70–120%) and precision (RSD < 20%) were obtained for most compounds in different types of water samples, spiked at two concentration levels [limit of quantification (LOQ) and 10LOQ]. Thus, surface water was spiked at 30 ng/L and 300 ng/L (amphetamine and amphetamine-like stimulants), 10 ng/L and 100 ng/L (cocaine and its metabolites), 300 ng/L and 3000 ng/L (tetrahydrocannabinol-COOH). Recovery experiments in effluent and influent wastewater were performed at spiking levels of three and fifteen times higher than the levels spiked in surface water, respectively. The validated method was applied to urban wastewater samples (influent and effluent). The acquisition of three selected reaction monitoring transitions per analyte allowed positive findings to be confirmed by accomplishment of ion ratios between the quantification transition and two additional specific confirmation transitions. In general, drug consumption increased in the weekends and during an important musical event. The highest concentration levels were 27.5 μg/L and 10.5 μg/L, which corresponded to 3,4-methylenedioxymethamphetamine (MDMA, or ecstasy) and to benzoylecgonine (a cocaine metabolite), respectively. The wastewater treatment plants showed good removal efficiency (>99%) for low levels of illicit drugs in water, but some difficulties were observed when high drug levels were present in wastewaters.