Hollow fiber liquid‐phase microextraction and determination of nonsteroidal anti‐inflammatories by capillary electrophoresis and sulfonamides by HPLC in human urine

In this paper two applications of three‐phase HF‐LPME for the determination of pharmaceuticals in human urine are proposed: a capillary electrophoresis with a photodiode array detection method for the analysis of seven nonsteroidal anti‐inflammatory drugs (NSAIDs) and a high‐performance liquid chromatographic with photo diode array and fluorescence detection method for the determination of four sulfonamides and their corresponding N⁴‐acetyl‐metabolites. Q3/2 Accurel® polypropylene hollow fibers were used for both procedures. Dihexyl ether was used as the supported liquid membrane for the determination of anti‐inflammatories and 1‐octanol for sulfonamides. An aqueous solution (pH 12) was used in both procedures as the acceptor phase and as the donor phase an aqueous solution (pH 2), and a 2 m Na₂SO₄ aqueous solution (pH 4) was used for the determination of the anti‐inflammatories and sulfonamides. The detection limits obtained were between 0.25 (naproxen) and 0.86 ng/mL (aceclofenac) for the determination of anti‐inflammatories and 7 × 10^?4 (sulfamethoxazole) and 0.048 ng/mL (N⁴‐acetyl‐sulfamethazine) for sulfonamides. The method was successfully applied to the determination of the analytes in human urine. Copyright © 2012 John Wiley & Sons, Ltd.     

Electrokinetic supercharging focusing in capillary zone electrophoresis of weakly ionizable analytes in environmental and biological samples

Five non‐steroidal anti‐inflammatory drugs, naproxen, fenoprofen, ketoprofen, diclofenac and piroxicam, were separated and analyzed by electrokinetic supercharging in CZE. Three different setups of the ITP technique were assayed for the separation and preconcentration of these five non‐steroidal anti‐inflammatory drugs. For the setup that gave the best results, we evaluated the influence of different parameters on separation and preconcentration efficiency such as sample pH, concentration of the leading stacker, BGE composition, electrokinetic injection time, composition and hydrodynamic injection of the solvent plug and of the terminating stacker. In the selected setup, the BGE (10 mM Na₂B₄O₇ + 50 mM NaCl in 10% of MeOH aqueous solution) contained the leading electrolyte while the terminating electrolyte, hydrodynamically injected after the sample (50 mbar×12 s), was 50 mM of CHES. Prior to sample injection at (700 s at −2 kV) a short plug of MeOH (50 mbar ×3 s) was hydrodynamically injected. The results show that this strategy enhanced detection sensitivity 2000‐fold compared with normal hydrodynamic injection, providing detection limits of 0.08 μg/L for standard samples with good repeatability (values of relative standard deviation, %RSD < 1.03%). Method validation with river water samples and human plasma demonstrated good linearity, with detection limits of 0.9 and 2 μg/L for river water samples and human plasma samples, respectively (as well as satisfactory precision in terms of repeatability and reproducibility).     

Simultaneous determination of non-steroidal anti-inflammatory drugs in river water by gas chromatography-mass spectrometry

The gas chromatography/mass spectrometric assay method was developed for the determination of 13 non‐steroidal anti‐inflammatory drugs (NSAIDs) in river water. Extraction was achieved by a liquid‐phase extraction procedure using methylene chloride. The extract was reacted for 30 min at 80°C based on the formation of methyl ester with 1.0 M HCl in methanol and extraction of the derivative with ethyl acetate, which was then measured by gas chromatography‐mass spectrometry. The limit of quantification of NSAIDs was 1.0–60 ng/L and the calibration curve showed linearity being greater than r=0.997. The method was used to analyze ten river water samples from various regions in Korea. Diclofenac, indoprofen, ketoprofen and loxoprofen were detected at concentration of up to 1.29 μg/L in river water. The developed method may prove valuable for use in the national monitoring project of NSAIDs in surface water.     

Simultaneous Determination of Ceftriaxone Sodium and Non Steroidal Anti‐Inflammatory Drugs in Pharmaceutical Formulations and Human Serum by RP‐HPLC

An accurate, sensitive and least time consuming reverse phase high performance liquid chromatographic (RP‐HPLC) method for the estimation of ceftriaxone in the presence of non steroidal anti‐inflammatory drugs in formulation and human serum has been developed and validated. Chromatographic separation was conducted on prepacked Purospher Star, C18 (5 μm, 250 × 4.6 mm) column at room temperature using methanol:water:acetonitrile (80:15:5 v/v/v) as a mobile phase, pH adjusted at 2.8 with ortho‐phosphoric acid and at a flow rate of 1.0 mL/minute, while UV detection was performed at 270 nm. The results obtained showed a good agreement with the declared content. The method shows good linearity in the range of 2.5‐25 μg/mL ceftriaxone serum concentrations with a correlation coefficient 0.999 (inter‐ and intra‐day RSD < 2.0%). The limit of detection and quantification for ceftriaxone and NSAID's in pharmaceutical formulation and serum were in the range 0.51‐1.54 μg/mL. Analytical recovery was >98.1%. The proposed method may be used for the quantitative analysis of commonly administered non steroidal anti‐inflammatory drugs i.e. tiaprofenic acid, naproxen sodium, flurbiprofen, diclofenac acid and mefenamic acid alone or in combination with ceftriaxone from raw materials, dosage formulations and in serum. The established HPLC method is rapid, accurate and selective, because of its sensitivity and reproducibility.     

Simultaneous Quantitation of Captopril and NSAID's in API,Dosage Formulations and Human Serum by RP‐HPLC

An accurate, sensitive and least time consuming reverse phase high performance liquid chromatographic (RP‐HPLC) method for the estimation of captopril in the presence of non steroidal anti‐inflammatory drugs in formulation and human serum has been developed and validated. Chromatographic separation was conducted on prepacked Purospher star C18 (5 μm, 25 × 0.46 cm) column at room temperature using methanol:water (80:20 v/v) as a mobile phase, pH adjusted at 2.8 with o‐phosphoric acid and at a flow rate of 1.0 mL min⁻¹, while UV detection was performed at 227 nm. The limit of detection and quantification for captopril were 1 and 0.35 ng mL⁻¹, while that for (NSAID's) i.e. flurbiprofen, ibuprofen, diclofenac sodium and mefenamic acid LOD were 0.2, 1, 2 and 0.4 ng mL⁻¹ respectively and LOQ were 0.9, 2.9, 8 and 1 ng mL⁻¹ Analytical recovery was > 98.1%. The method used for the quantitative analysis of commonly administered non steroidal anti‐inflammatory drugs (NSAID's) i.e. ibuprofen, flurbiprofen, diclofenac sodium and mefenamic acid alone or in combination with captopril from API (active pharmaceutical ingredients), dosage formulations and in human serum. The established method is rapid (RT < 12 min), accurate (recovery > 98.1%), selective (no interference of excepients and other commonly used drugs and food) and sensitive (LOQ 3.5 ng mL^;‐1) and reproducible (SD ± 0.003).     

Cover Picture: Electrophoresis 16'2011

Issue no. 16 is a regular issue with “Emphasis on Sensitivity Enhancement and Detection” consisting of 18 contributions distributed over 5 distinct parts and a Fast Track paper. The Fast Track paper is on “Barcoding of Giardia duodenalis isolates and derived lines from an established cryobank by a mutation scanning‐based approach”. The remaining 18 papers are grouped into 5 different parts. Part I and Part II represent the emphasis of this issue which involves “Sample Extraction and Enrichment and Sensitivity Enhancement” and “Detection Approaches” based on coupling CE with EC, ECL and MS. Part I has a series of 6 research papers on multifunctional magnetic nanoparticles for the enrichment of proteins, magnetic microspheres solid phase extraction of eight illegal drugs in human urine, hollow‐fiber liquid phase microextraction of nonsteroidal anti‐inflammatory drugs in wastewater, solid phase extraction to enhance sensitivity of CE for the determination of pharmaceuticals in river water, in‐line preconcentration CZE for the analysis of haloacetic acids in water, and dispersive liquid‐liquid microextraction coupled with CE for the determination of sulfonamides. Part II has 5 papers concerned with CE coupled with EC and ECL detection for the analysis of beta‐blockers, determination of nicotine and its metabolite cotinine in urine and cigarette samples by CE coupled with ECL, CE‐ECL detection for the analysis of ibandronate in drug formulation and human urine, CE‐ESI‐MS method for carbohydrate analysis, and analysis of phospholipids using MIP‐OTC in CEC‐ESI‐MS. Part III has 3 contributions on binding interaction and affinity capillary electrophoresis involving mobility shift assay for binding of DNA with NFAT3, rapid CE‐UV binding tests of environmentally hazardous compounds with polymer‐modified magnetic nanoparticles, and quantitative evaluation of lectin‐reactive glycoforms of alpha1‐acid glycoprotein using affinity CE with fluorescence detection. Part IV is on protein analysis by gel electrophoresis and has 2 contributions while Part V has 2 research papers on rice genotyping and determination of contrast agents by MEKC in urine and serum samples. Featured articles include: FAST TRACK: Barcoding of Giardia duodenalis isolates and derived lines from an established cryobank by a mutation scanning‐based approach. (( 10.1002/elps.201100283 )) Applications of multifunctional magnetic nanoparticles for the enrichment of proteins for PAGE separation. (( 10.1002/elps.201000657 )) Dispersive liquid‐liquid microextraction coupled with capillary electrophoresis for simultaneous determination of sulfonamides with the aid of experimental design. (( 10.1002/elps.201100142 )) Carbohydrate analysis by capillary electrophoresis‐microelectrospray ionization‐mass spectrometry. (( 10.1002/elps.201100027 )) Quantitative evaluation of lectin‐reactive glycoforms of α1‐acid glycoprotein using lectin affinity capillary electrophoresis with fluorescence detection. (( 10.1002/elps.201100146 )) High throughput functional marker assay for detection of Xa/xa and fgr genes in rice (Oryza sativa L.). (( 10.1002/elps.201100196 ))     

Capillary electrophoresis determination of nonsteroidal anti‐inflammatory drugs in wastewater using hollow fiber liquid‐phase microextraction

The presence of pharmaceuticals in the environment due to growing worldwide consumption has become an important problem that requires analytical solutions. This paper describes a CE determination for several nonsteroidal anti‐inflammatory drugs (ibuprofen, naproxen, ketoprofen, diclofenac, ketorolac, aceclofenac and salicylic acid) in environmental waters using hollow fiber membrane liquid‐phase microextraction. The extraction was carried out using a polypropylene membrane supporting dihexyl ether and the electrophoretic separation was performed in acetate buffer (30 mM, pH 4) using ACN as the organic modifier. Detection limits between 0.25 and 0.86 ng/mL were obtained, respectively. The method could be applied to the direct determination of the seven anti‐inflammatories in wastewaters, and five of them have been determined or detected in different urban wastewaters.     

On‐chip electromembrane extraction of acidic drugs

In the present work, a new supported liquid membrane (SLM) has been developed for on‐chip electromembrane extraction of acidic drugs combined with HPLC or CE, providing significantly higher stability than those reported up to date. The target analytes are five widely used non‐steroidal anti‐inflammatory drugs (NSAIDs): ibuprofen (IBU), diclofenac (DIC), naproxen (NAX), ketoprofen (KTP) and salicylic acid (SAL). Two different microchip devices were used, both consisted basically of two poly(methyl methacrylate) (PMMA) plates with individual channels for acceptor and sample solutions, respectively, and a 25 µm thick porous polypropylene membrane impregnated with the organic solvent in between. The SLM consisting of a mixture of 1‐undecanol and 2‐nitrophenyl octyl ether (NPOE) in a ratio 1:3 was found to be the most suitable liquid membrane for the extraction of these acidic drugs under dynamic conditions. It showed a long‐term stability of at least 8 hours, a low system current around 20 µA, and recoveries over 94% for the target analytes. NPOE was included in the SLM to significantly decrease the extraction current compared to pure 1‐undecanol, while the extraction properties was almost unaffected. Moreover, it has been successfully applied to the determination of the target analytes in human urine samples, providing high extraction efficiency.     

Preparation of highly hydrophilic magnetic nanoparticles with anion‐exchange ability and their application for the extraction of non‐steroidal anti‐inflammatory drugs in environmental samples

Diallyldimethylammonium chloride modified magnetic nanoparticles were synthesized by the “thiol‐ene” click chemistry reaction. Diallyldimethylammonium chloride rendered the material plenty of quaternary ammonium groups, and thus the excellent aqueous dispersibility and anion‐exchange capability. The novel material was then used as the magnetic solid‐phase extraction sorbent to extract eight non‐steroidal anti‐inflammatory drugs from water samples. Combined with high‐performance liquid chromatography and ultraviolet detection, under the optimal conditions, the developed method exhibited wide linearity ranges (1–1000, 2–1000, and 5–1000 ng/mL) with recoveries of 88.0–108.6% and low limits of detection (0.3–1.5 ng/mL). Acceptable precision was obtained with satisfactory intra‐ and inter‐day relative standard deviations of 0.4–4.4% (n = 3) and 1.1–5.5% (n = 3), respectively. Batch‐to‐batch reproducibility was acceptable with relative standard deviations <9.7%. The hydrophilic magnetic nanoparticle featured with quaternary ammonium groups showed high analytical potential for acidic analytes in environmental water samples.     

Multiclass and multiresidue screening of veterinary drugs and pesticides in infant formula using Quadrupole‐Orbitrap MS with PRM scan mode

A multiclass and multiresidue method for screening veterinary drugs and pesticides in infant formula was developed and validated using ultrahigh‐performance liquid chromatography coupled to Quadrupole‐Orbitrap high‐resolution mass spectrometry (UHPLC‐HRMS). A total of 49 veterinary drugs and pesticides investigated belong to 11 classes including antivirals, anticoccidials, macrolides, pyrethroids, insecticides, sulfonamides, beta‐agonists, sedatives, thyreostats, nonsteroidal anti‐inflammatory drugs, and other pharmacologically active substances. A generic sample preparation and highly selective acquisition mode of parallel reaction monitoring (PRM) were deliberately incorporated to perform efficient screening analysis. As a result, the screening target concentrations of the analytes varied from 1 to 500 μg/kg with ≤5% of false compliant rate as specified in Decision 2002/657/EC for screening analysis. The average recoveries ranged from 40.7 to 124.9% as well as the relative standard deviations from 4.2 to 26.6%, respectively. The matrix effects and interferences were effectively controlled by integrated application of dispersive solid phase extraction, PRM scan mode, and matrix‐matched standard calibration. The proposed method will be helpful to provide applicable strategy for screening residues in infant formula with surveillance purpose.     

Analgesic and Anti‐inflammatory Potential of Merged Pharmacophore Containing 1,2,4‐triazoles and Substituted Benzyl Groups via Thio Linkage

A plethora of non‐steroidal anti‐inflammatory drugs are available in the market with adverse side effects like gastrointestinal irritation, bleeding, and ulceration. Currently, the focus of researcher on the development of better, synergistic molecules by the hybridization of two or more active biomolecule or ligands to develop newer derivative possessing good anti‐inflammatory activity with minimum side effects. In line with this, the present study was designed to synthesize a series of merged pharmacophore contaning1,2,4‐triazoles and substituted benzyl groups via thio linkage. Purity of the derivatives was confirmed by thin‐layer chromatography, combustion analysis, and melting point. Structure of these derivatives was set up by determining infrared spectroscopy, nuclear magnetic resonance spectroscopy, and mass spectroscopy. All the synthesized derivatives were evaluated for their analgesic and anti‐inflammatory activities in mice and rats, respectively. In animal studies, the derivative 3‐(5‐(4‐nitrobenzylthio)‐4H‐1,2,4‐triazol‐3‐yl) pyridine showed more potent analgesic activity, and the derivative 3‐(5‐(2,4‐dimethylbenzylthio)‐4H‐1,2,4‐triazol‐3‐yl) pyridine showed more potent anti‐inflammatory activity as compared with other derivatives. The results of the present study indicate that reaction of pyridine linked 1,2,4‐triazole‐3‐thiol with different substituted benzyl halides to produce merged pharmacophore contaning1,2,4‐triazoles and substituted benzyl groups with potent analgesic and anti‐inflammatory activities. Docking studies were performed by using Argus lab, and all the derivatives exhibited good docking scores between −10 and −12 kcal/mol and were better as compared with standard drugs aspirin and indomethacin against cyclooxygenase‐2. Among all compounds, 3j has shown the maximum docking score and found in agreement to in pharmacological activities.     

Polystyrene‐Supported Core–Shell Beads with Aluminium MOF Coating for Extraction of Organic Pollutants

Aluminium‐based metal–organic framework (MOF) coatings on polystyrene bead surfaces were easily synthesized by reacting an intermediate metal hydroxide coating with an organic linker. Several different sizes of polystyrene beads were coated with aluminium metal hydroxide to construct Al@PS core–shell bead materials. The activated Al@PS core–shell beads were involved to make a homogenous MOF‐based layer in the presence of the organic linker. By using different sizes of the PS support the size of MOFs on the PS composites could be fine‐tuned under specific reaction conditions. MOF‐coated core–shell bead materials (Al‐1,4‐NDC@PS and MIL‐53(Al)@PS) were characterized using various analytical techniques. Al‐1,4‐NDC@PS and MIL‐53(Al)@PS were evaluated for solid‐phase microextraction (SPME) of hydrophobic polycyclic aromatic hydrocarbons (PAHs) and hydrophilic non‐steroidal anti‐inflammatory drugs (NSAIDs), respectively. Al‐1,4‐NDC@PS‐1000 displayed high extraction recoveries ranging from 79.2 % to 99.8 % in the SPME of PAHs. Meanwhile, MIL‐53(Al)@PS‐1000 showed 85.9–99.0 % extraction recoveries in the SPME of NSAIDs. These results show that the proposed approach holds potential to extract organic analytes on an industrial scale.     

Anti‐tumor platinum (IV) complexes bearing the anti‐inflammatory drug naproxen in the axial position

The role of inflammation in cancer generation is gaining importance in the field of cancer research. The chemo‐anti‐inflammatory strategy that involves using non‐steroidal anti‐inflammatory drug compounds as effective anti‐tumor agents is being acceded globally. In the present study, seven new Pt (IV) complexes based on cisplatin, carboplatin and oxaliplatin scaffold bearing the anti‐inflammatory drug naproxen in the axial position were synthesized and characterized by elemental analysis, ESI‐MS, Fourier transform‐infrared, ¹H‐ and ¹⁹⁵Pt‐NMR spectroscopy. The reduction behavior in the presence of ascorbic acid was studied using high‐performance liquid chromatography. The cytotoxicity against two human breast cell lines and the anti‐inflammatory properties were evaluated. All the complexes are able to promote a comparable activity, with average three‐ and 13‐fold more cytotoxic than cisplatin against MCF7 and MDA‐MB‐231 cell lines, respectively. The complexes show remarkable anti‐inflammatory effects, which indicated their potential in treating cancer associated with inflammation and reducing side‐effects of chemotherapy.     

One‐step hydrothermal synthesis of magnetic nitrogen‐doped graphene for magnetic solid‐phase extraction of nonsteroidal anti‐inflammatory drugs in environmental water samples

Graphene oxide has received extensive attention because of its unique properties and potential applications. In this study, magnetic nitrogen‐doped graphene was prepared by one‐step hydrothermal reaction using urea as the dopant and reductant, and ferroferric oxide nanoparticles were in situ deposited on the surface of the nanohybrids. The magnetic nitrogen‐doped graphene was characterized using various physical and chemical methods. It was used as a new adsorbent for the magnetic solid‐phase extraction of four nonsteroidal anti‐inflammatory drugs from the river water. The parameters influencing the extraction efficiency were optimized in detail. Under optimal conditions, this method provided a wide linear range (5–200 ng/mL). The limits of detection were in the range of 1.07–5.10 ng/mL. The recoveries varied from 81.2 to 121.5% with relative standard deviations of less than 10.8%. Overall, we can conclude that the proposed method offers an efficient pretreatment and enrichment and can be successfully applied for the extraction and determination of nonsteroidal anti‐inflammatory drugs in complex matrices.     

Synthesis and Molecular Recognition of Molecularly Imprinted Polymer with Ibuprofen as Template

Ibuprofen and ketoprofen are chemically similar non‐steroidal anti‐inflammatory drugs widely used in the treatment of arthritis. Using a molecular imprinting technique, a simple and rapid method was developed for the simultaneous separation and determination of ibuprofen and ketoprofen. Molecular imprinting introduces artificial binding sites into a synthetic polymer matrix, allowing it to exhibit selective rebinding of template molecules. Imprinted polymers can be regarded as an HPLC stationary phase, important for pharmaceutical analysis. Most molecularly imprinted polymers (MIPs) are synthesized by free radical polymerization of functional monomers, resulting in an excess of crosslinking monomers. In this study, MIPs have been prepared with a ibuprofen template, which can form intramolecular hydrogen bonds. Methacrylic acid (MAA) and ethyleneglycol dimethacrylate (EGDMA) were used as the functional monomer and cross‐linker, respectively. Bulk polymerization was carried out at 4 °C under UV radiation. The resulting MIP was ground into 25?44 μm particles, which were slurry‐packed into analytical columns. Template molecules were removed by methanol‐acetic acid (9:1, v/v). We evaluated the template binding performance of the MIP using HPLC, with ultraviolet (UV) detection at 234 nm. Chromatographic resolution of ibuprofen and ketoprofen on the MIPs were appraised using buffer/acetonitrile (45/55, v/v) as the mobile phase. Results show that the MIPs prepared using ibuprofen as the template had a significant molecular imprinting effect. The method was successfully applied to the separation and analysis of ibuprofen and ketoprofen in pharmaceuticals.     

Chromatographic behavior of a new hybrid type RP material containing silica bonded 1,3‐alternate 25,27‐bis‐[cyanopropyloxy]‐26,28‐bis‐[3‐propyloxy]‐calix[4]arene

A novel 1,3‐alternate 25,27‐bis‐[cyanopropyloxy]‐26,28‐bis‐[3‐propyloxy]‐calix[4]arene‐bonded silica gel stationary phase (CalixPrCN) was prepared and its structure was confirmed by ATR‐FTIR spectroscopy and elemental analysis. The CalixPrCN phase was characterized in terms of its surface coverage, hydrophobic selectivity, aromatic selectivity, shape selectivity, hydrogen bonding capacity, residue metal content, and silanol activity based on Tanaka, Lindner, and SMR 870 test protocols. The effect of the acetonitrile content on the retention and selectivity of the selected neutral, basic, and acidic solutes was studied. The neutral and acidic analytes exhibited classical RP behavior, in which retention time decreases with increasing acetonitrile content. In contrast, basic analytes showed an increase in retention at low and high percentages of acetonitrile, forming “U‐shaped” retention profiles. The new calixarene phase was compared with previously reported 1,3‐alternate 25,27‐bis‐[propyloxy]‐26,28‐bis‐[3‐propyloxy]‐calix[4]arene stationary phase and commercial cyanopropyl column. The results indicate that the CalixPrCN stationary phase behaves like RP packing; however, inclusion complex formation, dipole–dipole, and π–π interactions seem to be involved in the separation process. The selectivity of this phase was demonstrated in separation of polynuclear aromatic hydrocarbons, non‐steroidal anti‐inflammatory drugs, and sulfonamides as analytes.     

Ca(II), Sr(II) and Ba(II) ion interaction with the rheumatoid arthritis drug tenoxicam: Structural,thermal, and biological characterization

Recently, one of the most common conditions that manifests as joint and muscle inflammation is rheumatoid arthritis. One of the treatments for this arthritis includes non‐steroidal anti‐inflammatory drugs (NSAIDs) of the oxicam family, and the widest used drug in this family is tenoxicam (Tenox). In this study, the complexation properties of the drug Tenox with Ca(II), Sr(II) and Ba(II) ions in a (dichloromethane + water) binary solvent system are reported. The formed metal complexes were characterized structurally, thermally, and biologically. Tenox was found to act as a chelate monoanionic ligand towards all metal ions with complexation stoichiometry of 1:2 (Metal: Tenox) for Ca(II) and Sr(II) ions, and 1:1 for Ba(II) ions. The Tenox ligand behaves as a bidentate ligand when coordinated with Sr(II) or Ba(II) ions and as a tridentate ligand when coordinated with Ca(II) ions. The Sr(II) and Ba(II) complex of the Tenox ligand exhibited marked inhibitory effect on the cell growth of the C. albicans species.     

Determination of four acidic nonsteroidal anti‐inflammatory drugs in wastewater samples by dispersive liquid–liquid microextraction based on solidification of floating organic droplet and high‐performance liquid chromatography

A simple, environmentally friendly, and sensitive dispersive liquid–liquid microextraction based on solidification of floating organic droplet for the extraction of four acidic nonsteroidal anti‐inflammatory drugs (ketoprofen, naproxen, ibuprofen, and diclofenac) from wastewater samples subsequent by high‐performance liquid chromatography analysis was developed. The influence of extraction parameters such as pH, the effect of solution ionic strength, type of extraction solvent, disperser solvent, and extraction solvent volume were studied. High enrichment factors (283–302) were obtained through the developed method. The method provides good linearity (r > 0.999) in a concentration range of 1–100 μg/L, good intra‐ and inter‐day precision (relative standard deviation < 7%) and low limits of quantification. The relative recoveries of the selected compounds were situated over 80% both in synthetic and real water samples. The developed method has been successfully applied for the analysis of the selected compounds in wastewater samples.     

Multi‐residue analysis of 44 pharmaceutical compounds in environmental water samples by solid‐phase extraction coupled to liquid chromatography‐tandem mass spectrometry

A solid‐phase extraction combined with a liquid chromatography‐tandem mass spectrometry analysis has been developed and validated for the simultaneous determination of 44 pharmaceuticals belonging to different therapeutic classes (i.e., antibiotics, anti‐inflammatories, cardiovascular agents, hormones, neuroleptics, and anxiolytics) in water samples. The sample preparation was optimized by studying target compounds retrieval after the following processes: i) water filtration, ii) solid phase extraction using Waters Oasis HLB cartridges at various pH, and iii) several evaporation techniques. The method was then validated by the analysis of spiked estuarine waters and wastewaters before and after treatment. Analytical performances were evaluated in terms of linearity, accuracy, precision, detection, and quantification limits. Recoveries of the pharmaceuticals were acceptable, instrumental detection limits varied between 0.001 and 25 pg injected and method quantification limits ranged from 0.01 to 30.3 ng/L. The precision of the method, calculated as relative standard deviation, ranged from 0.3 to 49.4%. This procedure has been successfully applied to the determination of the target analytes in estuarine waters and wastewaters. Eight of these 44 pharmaceuticals were detected in estuarine water, while 26 of them were detected in wastewater effluent. As expected, the highest values of occurrence and concentration were found in wastewater influent.     

Application of column‐switching HPLC method in evaluating pharmacokinetic parameters of zaltoprofen and its salt

The objective of this study was to compare the pharmacokinetic parameters of zaltoprofen and those of its sodium salt in rats. Zaltoprofen, a potent non‐steroidal anti‐inflammatory agent, was virtually insoluble in water, but its sodium salt had excellent water solubility. To investigate the effect of aqueous solubility differences upon their pharmacokinetic parameters, minicapsules containing the drug powders were administrated orally to rats, and blood samples were taken via the common carotid artery. A column‐switching high‐performance liquid chromatographic analytical procedure was developed and validated for the quantitation of zaltoprofen in rat plasma samples. Our study demonstrated that the time required to reach maximum plasma concentration (T_max) of zaltoprofen sodium was significantly reduced and its maximum plasma concentration (C_max) was increased 1.5‐fold, relative to the values for zaltoprofen. It is anticipated that the sodium salt of zaltoprofen will allow the rapid onset of the drug's action in the treatment of inflammatory diseases. Copyright © 2008 John Wiley & Sons, Ltd.