Pigeon Pea Husk for Removal of Emerging Contaminants Trimethoprim and Atenolol from Water.

The pace of industrialization and rapid population growth in countries such as India entail an increased input of industrial and sanitary organic micropollutants, the so-called emerging contaminants (EC), into the environment. The emission of EC, such as pharmaceuticals, reaching Indian water bodies causes a detrimental effect on aquatic life and ultimately on human health. However, the financial burden of expanding sophisticated water treatment capacities renders complementary, cost-efficient alternatives, such as adsorption, attractive. Here we show the merits of washed and milled pigeon pea husk (PPH) as low-cost adsorbent for the removal of the EC trimethoprim (TMP) and atenolol (ATN) that are among the most detected pharmaceuticals in Indian waters. We found a linear increase in adsorption capacity of PPH for TMP and ATN at concentrations ranging from 10 to 200 µg/L and from 50 to 400 µg/L, respectively, reflecting the concentrations occurring in Indian water bodies. Investigation of adsorption kinetics using the external mass transfer model (EMTM) revealed that film diffusion resistance governed the adsorption process of TMP or ATN onto PPH. Moreover, analysis of the adsorption performance of PPH across an extensive range of pH and temperature illustrated that the highest adsorption loadings achieved concurred with actual conditions of Indian waters. We anticipate our work as starting point towards the development of a feasible adsorbent system aiming at low-cost water treatment.

Dispersive solid-phase extraction of racemic drugs using chiral ionic liquid-metal-organic framework composite sorbent.

Nowadays, enantioseparation of racemic pharmaceuticals in preparations is a prime concern by drug authorities across the globe. In the present work, it was attempted to develop novel enantioselective extraction method for five clinically used drugs (atenolol, propranolol, metoprolol, racecadotril, and raceanisodamine in their tablets) as racemates. The enantioselective solid-liquid extraction of these racemic drugs was carried out successfully by the use of chiral ionic liquid (CIL) in combination with a metal organic framework (MOF) for the first time. The composite CIL@MOF was synthesized from tropine based chiral ionic liquids with L-proline anion ([CnTr][L-Pro], n=3-6) and HKUST-1 type MOF, which was comprehensively characterized before being used as sorbent for enantioselective dispersive solid-liquid extraction. Preliminary selection of appropriate CIL was carried out on thin layer chromatography (TLC); under the joint participation of copper ion in the developing reagent, [C3Tr][L-Pro] ionic liquid showed better resolution performance with ΔRf value of 0.35 between the enantiomers was obtained for racemic atenolol. Moreover, the effect of copper salt dosage, amount of CIL, soli-liquid ratio and extraction time were investigated. The optimal conditions were obtained after thorough investigations; i.e. sample solution: ethanol, elution solvent: methanol, solid-liquid ratio: 12.5 mg:50 mL, amount of copper salt: 8 mg L-1, amount of impregnated CIL: 30% and extraction time of 30 min. As a result, enantiomeric excess values are 90.4%, 95%, 92%, 81.6% and 83.2% for atenolol, propranolol, metoprolol, racecadotril and raceanisodamine, respectively. The developed enantioselective method was validated following ICH guidelines and it was proved to be simple, effective and enantioselective way for separation of racemic pharmaceuticals with similar behaviors.

Ozonation as a pretreatment process for nanofiltration brines: Monitoring of transformation products and toxicity evaluation.

Considerable interest has been given to using nanofiltration (NF) in lieu of reverse osmosis for water reclamation schemes due to lower energy consumption, higher flux rates while ensuring good micropollutants rejection. The application NF results in the generation of a large concentrated waste stream. Treatment of the concentrate is a major hurdle for the implementation of membrane technologies since the concentrate is usually unusable due to a large pollutants content. This work focuses on the application of ozonation as pretreatment of urban NF concentrates, the generation of transformation products and their relative toxicity. Three pharmaceutical micropollutants largely encountered in water cycle were selected as target molecules: acetaminophen, carbamazepine and atenolol. Through accurate-mass Q-TOF LC-MS/MS analyses, more than twenty ozonation products were detected, structure proposals and formation pathways were elaborated. Attempts were made to understand the correlation between the transformation products and acute toxicity on Vibrio fischeri strain. It is the first time that an integrated study reported on the ozonation of pharmaceuticals in urban membrane concentrates, in terms of transformation products, kinetics, degradation mechanisms, as well as toxicity assessment.

Factors screening to statistical experimental design of racemic atenolol kinetic resolution via transesterification reaction in organic solvent using free Pseudomonas fluorescens lipase.

As the (R)-enantiomer of racemic atenolol has no ß-blocking activity and no lack of side effects, switching from the racemate to the (S)-atenolol is more favorable. Transesterification of racemic atenolol using free enzymes investigated as a resource to resolve the racemate via this method is limited. Screenings of enzyme, medium, and acetyl donor were conducted first to give Pseudomonas fluorescens lipase, tetrahydrofuran, and vinyl acetate. A statistical design of the experiment was then developed using Central Composite Design on some operational factors, which resulted in the conversions of 11.70-61.91% and substrate enantiomeric excess (ee) of 7.31-100%. The quadratic models are acceptable with R2 of 95.13% (conversion) and 89.63% (ee). The predicted values match the observed values reasonably well. Temperature, agitation speed, and substrate molar ratio factor have low effects on conversion and ee, but enzyme loading affects the responses highly. The interaction of temperature-agitation speed and temperature-substrate molar ratio show significant effects on conversion, while temperature-agitation speed, temperature-substrate molar ratio, and agitation speed-substrate molar ratio affect ee highly. Optimum conditions for the use of Pseudomonas fluorescens lipase, tetrahydrofuran, and vinyl acetate were found at 45°C, 175 rpm, 2000 U, and 1:3.6 substrate molar ratio.

Competition and enhancement effect in coremoval of atenolol and copper by an easily regenerative magnetic cation exchange resin.

This paper aimed to investigate the removal of combined Cu2+ and atenolol (ATL) in aqueous solution by using a newly synthesized magnetic cation exchange resin (MCER) as the adsorbent. The MCER exhibited efficient removal performance in sole, binary, pre-loading and saline systems. The adsorption kinetics of Cu2+ and ATL fitted both pseudo-first-order and pseudo-second order model, while better described by pseudo-second order model in binary system. In mixed Cu2+ and ATL solution, the adsorption of ATL was suppressed due to direct competition of carboxylic groups, while Cu2+ adsorption was enhanced because of the formation of surface complexes. This increasing in heterogeneity was demonstrated by adsorption isotherms, which were more suitable for Freundlich model in binary system, while better described by Langmuir model in sole system. As proved by FTIR and XPS spectra, both amino and hydroxyl groups of ATL could form complexes with Cu2+. Decomplexing-bridging interaction was elucidated as the leading mechanism in coremoval of Cu2+ and ATL, which involved [Cu-ATL] decomplexing and newly created Cu- or ATL sites for additional bridging. For saline system, the resulting competition and enhancement effects in mixed solution were amplified with the addition of co-existing cations. Moreover, the MCER could be effectively regenerated by 0.01 M HCl solution and maintain high stability over 5 adsorption-desorption cycles, which render it great potential for practical applications.

Liquid chromatographic enantioseparation of three beta-adrenolytics using new derivatizing reagents synthesized from (S)-ketoprofen and confirmation of configuration of diastereomers.

Diastereomers of racemic ß-adrenolytic drugs [namely (RS)-propranolol, (RS)-metoprolol and (RS)-atenolol] were synthesized under microwave irradiation with (S)-ketoprofen based chiral derivatization reagents (CDRs) newly synthesized for this purpose. (S)-Ketoprofen was chosen for its high molar absorptivity (εo ~ 40,000) and its availability as a pure (S)-enantiomer. Its -COOH group was activated with N-hydroxysuccinimide and N-hydroxybenzotriazole; these were easily introduced and also acted as good leaving groups during nucleophilic substitution by the amino group of the racemic ß-adrenolytics. The CDRs were characterized by UV, IR, 1 H-NMR, HRMS and CHNS. Separation of diastereomers was achieved by RP HPLC and open column chromatography. Absolute configuration of the diastereomers was established with the help of 1 HNMR supported by developing their optimized lowest energy structures using Gaussian 09 Rev. A.02 program and hybrid density functional B3LYP with 6-31G* basis set (based on density functional theory), and elution order was established. RP HPLC conditions for separation were optimized and the separation method was validated. The limit of detection values were 0.308 and 0.302 ng mL-1 . Copyright © 2016 John Wiley & Sons, Ltd.

A novel pure component contribution algorithm (PCCA) for extracting components' contribution from severely overlapped signals; an application to UV-spectrophotometric data.

A novel, simple and accurate algorithm capable of extracting the contribution of each component from a mixture signal where the components are completely overlapped was developed. It is based on the development of a coded function which eliminates the signal of interfering components using mean centering as a processing tool; finally the pure contribution of each component is extracted. The algorithm allows the determination of each component as a single one. It was validated by the use of simulated data set of three overlapped signals and tested against simulated random noise. Two fit values were developed and calculated for optimization, one to test that that the absorptivity values of the extracted spectra are within the confidence limits of the slope and the other is the correlation between the pure and extracted spectra. It has been successfully applied to real UV data of binary mixture of Ibuprofen and Paracetamol and ternary mixture of Amiloride hydrochloride, Atenolol and Hydrochlorothiazide in tablets and capsules, respectively. The results were compared to previously reported separation method and no significant difference was found regarding both accuracy and precision.

Study of the enantioseparation capability of chiral dual system based on chondroitin sulfate C in CE.

It has been reported that chiral dual system is able to improve the enantioseparation of enantiomers in many cases. Currently, the dual systems involved in CE chiral separation are mostly dual CDs systems, and the polysaccharides-based chiral dual system was reported in only one paper. To the best of our knowledge, the use of chondroitin sulfate C (CSC)-based dual system for enantiomeric separation has not been reported previously. Herein, four CSC-based chiral dual systems, namely CSC/glycogen, CSC/chondroitin sulfate A (CSA), CSC/hydroxypropyl-ß-CD (HP-ß-CD), as well as CSC/ß-CD (ß-CD), were evaluated for the first time for their enantioseparation capability by CE in this paper. During the course of the work, the influences of chiral selector concentration and buffer pH values on enantioseparation in dual systems were systematically investigated. Under the optimized conditions, the dual system consisting of CSC and glycogen exhibited better separations toward nefopam, duloxetine, sulconazole, atenolol, laudanosine, and cetirizine enantiomers compared to the single CSC or glycogen system. The combination of CSC and HP-ß-CD improved the separation of amlodipine and chlorphenamine enantiomers. However, no synergistic effect was observed in the CSC/CSA and CSC/ß-CD systems.

Enantiomer separations of basic chiral compounds by capillary electrochromatography on a phosphated ß-cyclodextrin-modified zirconia monolith.

Phosphated ß-cyclodextrin (PCD)-coated zirconia monolith was used as the chiral stationary phase in capillary electrochromatography (CEC) for separation of four basic chiral compounds including metoprolol (MET), sertraline (SER), citalopram (CIT) and atenolol (ATE). Migration, chiral selectivity and resolution data were measured in reversed-phase mobile phases of varying pH, buffer and organic modifier compositions. Optimum mobile phase conditions for CEC separation of the compounds studied were found to be a 15-mM aqueous buffer of pH 5.0 with 5mM PCD. Baseline separations of enantiomers of CIT, MET and SER, and partial separation for ATE were achieved with the optimal mobile phase.

Photo-Fenton decomposition of ß-blockers atenolol and metoprolol; study and optimization of system parameters and identification of intermediates.

Active pharmaceutical compounds reach the wastewater treatment plants mainly through excretion and improper disposal, and, because of insufficient treating methods, they end up to surface water or even potable water in some cases. Atenolol and metoprolol are ß-blockers, members of cardiovascular pharmaceuticals group. They are generally used in the treatment of disorders such as hypertension, angina and arrhythmias. They have been in long-term use in Europe and North America, and they have also been detected in the aquatic environment. In this study the degradation of atenolol and metoprolol in aqueous solutions by means of the photo-Fenton reaction was investigated. The purpose of this study was: (i) to investigate the influence of the concentrations of iron and hydrogen peroxide, by means of central composite design, (ii) to study the degradation kinetics in aqueous solutions, (iii) to evaluate the mineralization and the toxicity evolution of the target compounds and (iv) to identify the degradation products. It has been found that increase of iron and hydrogen peroxide concentration accelerate the degradation of atenolol and metoprolol, while the kinetics of the process can be characterized as pseudo-first order. In general the photo-Fenton method has proved to be effective in decomposing and mineralizing the target compounds. The determination of the by-products formed during the degradation using LC-MS/MS equipment and the evaluation of the toxicity of the treated solution in different stages of the process would offer significant, innovative information regarding the treatment of water and wastewater containing active pharmaceutical compounds, especially of the ß-blocker group.

A novel solid-phase extraction-spectrofluorimetric method for the direct determination of atenolol in human urine.

A novel, simple, sensitive and selective solid-phase extraction (SPE)-spectrofluorimetric method has been developed for the determination of atenolol (ATE) in human urine. Because an extraction procedure is required to isolate ATE or eliminate the interfering molecules present in complex human urine for the direct spectrofluorimetric determination, a pH-sensitive poly(acrylic acid-ethylene glycol dimethacrylate) [poly(AA-EGDMA)] hydrogel was developed and used as a SPE adsorbent. Some factors affecting the ATE extraction efficiency, such as washing solvent type and volume, and the volume of elution solvent were optimized. Eluates from SPE cartridges were analyzed using a spectrofluorimeter (λ(ex) = 277 nm and λ(em) = 300 nm). The calibration graph was linear over the concentration range 0.15-4.0 µg/mL. Limit of detection (LOD) and limit of quantification (LOQ) values were found to be 0.03 and 0.10 µg/mL, respectively. Relatively high intraday [2.06%, mean relative standard deviation (RSD)] and interday (2.6%, mean RSD) precisions were achieved. High mean recovery (95.4%) and low RSD values (3.8%) were obtained for spiked ATE in human urine. The spectrofluorimetric method presented here can be easily applied to assay trace amounts of ATE in pharmaceuticals and biological samples.

Microfluidic chip capillary electrophoresis coupled with electrochemiluminescence for enantioseparation of racemic drugs using central composite design optimization.

Optimization based on central composite design (CCD) for enantioseparation of anisodamine (AN), atenolol (AT), and metoprolol (ME) in human urine was developed using a microfluidic chip-CE device. Coupling the flexible and wide working range of microfluidic chip-CE device to CCD for chiral separation of AN, AT, and ME in human urine, a total of 15 experiments is needed for the optimization procedure as compared to 75 experiments using the normal one variable at a time optimization. The optimum conditions obtained are found to be more robust as shown by the curvature effects of the interaction factors. The developed microfluidic chip-CE-ECL system with adjustable dilution ratios has been validated by satisfactory recoveries (89.5-99% for six enanotiomers) in urine sample analysis. The working range (0.3-600 µM), repeatability (3.1-4.9% RSD for peak height and 4.0-5.2% RSD for peak area), and detection limit (0.3-0.6 µM) of the method developed are found to meet the requirements for bedside monitoring of AN, AT, and ME in patients under critical conditions. In summary, the hyphenation of CCD with the microfluidic chip-CE device is shown to offer a rapid means for optimizing the working conditions on simultaneous separation of three racemic drugs using the microfluidic chip-CE device developed.

Multivariate curve resolution-alternating least squares assisted by voltammetry for simultaneous determination of betaxolol and atenolol using carbon nanotube paste electrode.

In the present work differential pulse voltammetry coupled with multivariate curve resolution-alternating least squares (MCR-ALS) was applied for simultaneous determination of betaxolol (Bet) and atenolol (Ate) in 0.20 M Britton-Robinson (B-R) buffer solution at the surface of a multi-walled carbon nanotube modified carbon paste electrode (MWCNT/CPE). Characterization of the modified electrode was carried out by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV). A strategy based on experimental design was followed. Operating conditions were improved with central composite rotatable design (CCRD) and response surface methodology (RSM), involving several chemical and instrumental parameters. Then second order data were built from variable pulse heights of DPV and after correction in potential shift analyzed by MCR-ALS. Analytical parameters such as linearity, repeatability, and stability were also investigated and a detection limit (DL) of 0.19 and 0.29 µM for Bet and Ate was achieved, respectively. The proposed method was successfully applied in simultaneous determining the two analytes in human plasma.

[Photodegradation of atenolol in aqueous nitrate solution].

The aqueous photolysis of beta-blocker atenolol (ATL) using Xe lamp as simulated solar irradiation source was investigated in the presence of nitrate ions. The effects of nitrate ion concentration, solution pH value, and concentration of bicarbonate and humic substance on the photodegradation of ATL were studied. The results showed that photodegradation of ATL in nitrate solution followed pseudo-first-order kinetics. The increasing concentration of nitrate ion promoted the photodegradation rate of ATL. The first-order rate constant increased from 0.002 26 min(-1) to 0.009 4 min(-1) with nitrate concentration increasing from 0 to 5 mmol x L(-1). Acidic or alkaline condition of the solution favored the photodegradation of ATL. Different concentration of bicarbonate showed insignificant effect of the degradation while the increasing concentration of fulvic acid showed inhibiting effect. Hydroxyl radical was determined to be formed during the photolysis process of ATL using isopropanol as molecular probe. The main photoproducts of ATL were identified by using SPE-LC-MS techniques and possible photoinduced degradation pathways in nitrate solution were proposed.

Chromatographic comparison of atenolol separation in reaction media on cellulose tris-(3,5-dimethylphenylcarbamate) chiral stationary phase using ultra fast liquid chromatography.

Because chiral liquid chromatography (LC) could become a powerful tool to estimate racemic atenolol quantity, excellent enantiomeric separation should be produced during data acquisition for satisfactory observation of atenolol concentrations throughout the racemic resolution processes. Selection of chiral LC column and analytical protocol that fulfill demands of the ultra fast LC analysis is essential. This article describes the characteristics of atenolol chromatographic separation that resulted from different resolution media and analytical protocols with the use of a Chiralcel® OD column. The chromatograms showed quite different characteristics of the separation process. The single enantiomer and racemic atenolol could be recognized by the Chiralcel® OD column in less than 20 min. Symmetrical peaks were obtained; however, several protocols produced peaks with wide bases and slanted baselines. Observations showed that efficient enantioresolution of racemic atenolol was obtained at slow mobile phase flow rate, decreased concentration of amine-type modifier but increased alcohol content in mobile phase and highest ultraviolet detection wavelength were required. The optimal ultra fast LC protocol enables to reduce and eliminate the peaks of either the atenolol solvent or the buffers and provided the highest peak intensities of both atenolol enantiomers.

Reaction of ß-blockers and ß-agonist pharmaceuticals with aqueous chlorine. Investigation of kinetics and by-products by liquid chromatography quadrupole time-of-flight mass spectrometry.

The degradation of two ß-blockers (atenolol and propranolol) and one ß-receptor agonist (salbutamol) during water chlorination was investigated by liquid chromatography-mass spectrometry (LC-MS). An accurate-mass quadrupole time-of-flight system (QTOF) was used to follow the time course of the pharmaceuticals and also used in the identification of the by-products. The degradation kinetics of these drugs was investigated at different concentrations of chlorine, bromide and sample pH by means of a Box-Behnken experimental design. Depending on these factors, dissipation half-lives varied in the ranges 68-145 h for atenolol, 1.3-33 min for salbutamol and 42-8362 min for propranolol. Normally, an increase in chlorine dosage and pH resulted in faster degradation of these pharmaceuticals. Moreover, the presence of bromide in water samples also resulted in a faster transformation of atenolol at low chlorine doses. The use of an accurate-mass high-resolution LC-QTOF-MS system permitted the identification of a total of 14 by-products. The transformation pathway of ß-blockers/agonists consisted mainly of halogenations, hydroxylations and dealkylations. Also, many of these by-products are stable, depending on the chlorination operational parameters employed.

Micellar electrokinetic chromatography with acid labile surfactant.

We present a study of a degradable surfactant, sodium 4-[(2-methyl-2-undecyl-1,3-dioxolan-4-yl)methoxy]-1-propane sulfonate that is also known as an acid-labile surfactant (ALS). The performance of ALS as a pseudostationary phase is assessed and compared with established pseudostationary phases such as sodium dodecyl sulphate (SDS), volatile surfactants and polymeric micelles. ALS achieves separation efficiency of 100,000-145,000 theoretical plates and relative standard deviation (RSD) of electrophoretic mobility (n=5) of less than 3%. Retention factors with ALS are strongly correlated with those with SDS. This is shown by the R2=0.79 for all eleven analytes and an R2=0.992 for specifically the non-hydrogen bonding (NHB) analytes. However, ALS displays different selectivity than SDS for hydrogen bond donor (HBD) and hydrogen bond acceptor (HBA) solutes (R2 of 0.74 and 0.88, respectively). ALS is degraded to less surface active compounds in acidic solution. These less surface-active compounds are more compatible with the electrospray ionization mass spectrometry (ESI-MS). ALS has a half-life of 48 min at pH 4. ALS has the potential to couple micellar electrokinetic chromatography (MEKC) with the ESI-MS. ALS can be used as a pseudostationary phase for a high efficiency separation and later acid hydrolyzed to enable an ESI-MS analysis.

A highly sensitive LC-MS/MS method capable of simultaneously quantitating celiprolol and atenolol in human plasma for a cassette cold-microdosing study.

A highly sensitive simultaneous quantitative method for a cassette cold-microdosing study on celiprolol and atenolol was developed with liquid chromatography-tandem mass spectrometry. The method utilizes a combination of solid-phase extraction (SPE) with strong cation exchange (SCX) cartridge columns and reversed-phase chromatography with an ODS analytical column. SCX-SPE cartridge columns (100 mg sorbent) were used for a selective extraction of celiprolol, atenolol and metoprolol (internal standard) from 500 µL of human plasma samples. Turbo-ion spray at positive mode was employed for the ionization of the drug compounds. Quantitation was performed on a triple quadrupole mass spectrometer by selected reaction monitoring with the transitions of m/z 380 to m/z 251 for celiprolol and m/z 267 to m/z 145 for atenolol. Separation of analytes was achieved on an ODS column (100 mm length × 2.1 mm id, 3 µm) by a gradient elution with 10 mM formic acid and methanol by varying their proportion at a flow rate of 0.2 mL/min. The method was validated in the range of 1-250 pg/mL for celiprolol and 2.5-250 pg/mL for atenolol and was successfully applied to the elucidation of pharmacokinetic profiling in a cold cassette microdosing study of the ß-blockers.

Determination of atenolol in human urine by gas chromatography-mass spectrometry method.

A sensitive and efficient method was developed for the determination of atenolol in human urine by gas chromatography-mass spectrometry (GC-MS). Atenolol and metoprolol (internal standard, IS) were extracted from human urine with a mixture of chloroform and butanol at basic pH with liquid-liquid extraction. The extracts were derivatized with N-Methyl-N-(trimethylsilyl)trifluoroacetamide (MSTFA) and analyzed by GC-MS using a capillary column. The standard curve was linear (r = 0.99) over the concentration range of 50-750 ng/mL. Intra- and inter-day precision, expressed as the relative standard deviation were less than 5.0%, and accuracy (relative error) was better than 7.0%. The analytical recovery of atenolol from human urine has averaged 91%. The limit of quantification was 50 ng/mL. Also, the method was successfully applied to a patient with hypertension who had been given an oral tablet of 50 mg atenolol.

Occurrence and removal of pharmaceuticals and hormones through drinking water treatment.

The occurrence of fifty-five pharmaceuticals, hormones and metabolites in raw waters used for drinking water production and their removal through a drinking water treatment were studied. Thirty-five out of fifty-five drugs were detected in the raw water at the facility intake with concentrations up to 1200 ng/L. The behavior of the compounds was studied at each step: prechlorination, coagulation, sand filtration, ozonation, granular activated carbon filtration and post-chlorination; showing that the complete treatment accounted for the complete removal of all the compounds detected in raw waters except for five of them. Phenytoin, atenolol and hydrochlorothiazide were the three pharmaceuticals most frequently found in finished waters at concentrations about 10 ng/L. Sotalol and carbamazepine epoxide were found in less than a half of the samples at lower concentrations, above 2 ng/L. However despite their persistence, the removals of these five pharmaceuticals were higher than 95%.