Mussel‐inspired method to decorate commercial nanofiltration membrane for heavy metal ions removal

Nanofiltration (NF) membranes have been widely used for the treatment of electroplating, aerospace, textile, pharmaceutical, and other chemical industries. In this work, halloysite nanotubes (HNTs) were directly anchored on the surface of commercial nanofiltration (NF) membrane by dopamine modification following advantageous bio‐inspired methods. SEM and AFM images were used to characterize the HNTs decorated membrane surface in terms of surface morphology and roughness. Water contact angle (WCA) was employed in evidencing the incorporation of HNTs and dopamine in terms of hydrophilicity or hydrophobicity. Augmentation of HNTs was found to obviously enhance the hydrophilicity and surface roughness resulting in improved water permeability of membrane. More importantly, the rejection ratios of membrane also increased during the removal of heavy metal ions from wastewater. The permeability and Cu²⁺ rejection ratio of modified NF membrane were as high as 13.9 L·m^?2·h^?1·bar^?1 and 74.3%, respectively. Incorporation of HNTs was also found to enhance the anti‐fouling property and stability of membrane as evident from long‐term performance tests. The relative concentration of HNTs and dopamine on membrane surface was optimized by investigating the trade‐off between water permeability and rejection ratio.     

Preparation and characterization of polyethersulfone/silver nanocomposite ultrafiltration membrane for antibacterial applications

Antimicrobial ultrafiltration membranes were prepared by coating silver nanoparticles on the surface of polyethersulfone (PES) membranes which were fabricated via phase inversion induced by the immersion precipitation technique, and their morphology and performance were compared with the antimicrobial PES membranes synthesized by adding the silver nanoparticles into the casting solution during the phase inversion process. For this purpose, stable and uniform colloidal solutions of the silver nanoparticles were prepared by chemical reduction of silver salt using fructose and dimethylformamide as a reducing agent. The silver nanoparticles were characterized by ultraviolet–visible spectroscopy, X‐ray powder diffraction and dynamic light scattering analysis. The morphology and surface properties of the prepared membranes were examined by field emission scanning electron microscopy and atomic force microscopy analysis. Moreover, the separation properties, antimicrobial efficiency and amount of silver release from the PES nanocomposite membranes during the cross flow ultrafiltration were determined. The results indicated that the silver content of the coated PES membranes was greater than the membranes fabricated by the solution blending method. Also, the permeation flux of the silver‐coated membranes was similar to the neat PES membranes, while the membranes prepared by the second approach had less flux. The membranes synthesized by both coating and blending methods showed high antimicrobial and bactericidal activity against gram‐negative bacteria such as Escherichia coli and gram‐positive bacteria such as Staphylococcus aureus. Finally, the prepared antimicrobial membranes were successfully used for the ultrafiltration of raw milk to reduce the microbial load during the concentration process. Copyright © 2014 John Wiley & Sons, Ltd.     

Synthesis and characterization of heterocyclic functionalized polymers by click reaction: Preparation of magnetic nanocomposites and studies on their thermal,mechanical, photophysical and metal ions removal properties

This work reports synthesis and characterization of heterocyclic functionalized polymers, poly(triazole-etherimidazole)s(PTAEI), from a dialkyne-terminated compound, 3-(4,5-bis(4-(propargyloxy)phenyl)-1H-imidazol-2-yl)-9-ethyl-9H-carbazole, by using click reaction. PTAEIs were characterized and their properties such as solubility, thermal, mechanical, photophysical and metal ions adsorption were investigated. These polymers had weight average molar masses(Mw) in the range of 19100-26700 g/mol, exhibited excellent solubility in polar aprotic solvents and formed low-colored flexible thin films by solution casting method. They exhibited good thermal stability with glass transition temperatures(Tg) between 160 °C and 211 °C and 10% weight loss temperatures(T10%) in the range of 308-426 °C. Nanocomposites of PTAEIs with epoxide-terminated Fe3O4 showed that strong interfacial interaction between inorganic particles and the polymer matrix contributed to the enhanced thermal and mechanical properties. The photoluminescence intensity of the PTAEIs increased and the spectra red shifted with increasing Fe3O4 content. The PTAEIs and nanocomposites were tested for their extraction capability of metal ions from aqueous solutions either individually or in the mixture.     

Synthesis and characterisation of magnetic activated carbon/diopside nanocomposite for removal of reactive dyes from aqueous solutions: experimental design and optimisation

In this work, a series of magnetic activated carbon/nanodiopside (Fe₃O₄/AC/Diop) nanocomposites were synthesised and used for the removal of reactive green KE-4BD dye from the aqueous solution. After preparation of nanodiopside by sol-gel method and activated carbon from coconut husk, first, Fe₃O₄/AC composite was prepared by in situ synthesis of Fe₃O₄ nanoparticles between activated carbon pores, and then, different percentages of Fe₃O₄/AC/Diop nanocomposites were prepared by simple mixing of Fe₃O₄/AC composite and Diop in ethanol. Formation of Fe₃O₄/AC and Fe₃O₄/AC/Diop composites was characterised by FTIR, field emission scanning electron microscopy, BET, XRD and vibrating sample magnetometer analyses. Thermogravimetric analysis was used to show the adsorption capacity of the adsorbent more accurately. Effects of amount of adsorbent, initial pH, contact time and dye concentration on reactive green dye removal were also studied using central composite design. Optimal conditions for maximum reactive green KE-4BD dye adsorption (98.35%) process were as follows: pH= 4.90, adsorbent amount: 0.015 g, dye concentration: 37.17 mg/L and contact time: 10.12 min, respectively. In addition, the adsorption kinetics, thermodynamics and isotherms were examined. Adsorption isotherms (q_max: 344.827 mg/g), kinetics and thermodynamics were demonstrated that the sorption processes were better described by the pseudo-second-order equation and the Langmuir equation.     

Synthetic functionalized terpolymeric resin for the removal of hazardous metal ions: synthesis,characterization and batch separation analysis

An effectual functionalized synthetic resin involving anthranilic acid/4‐nitroaniline/formaldehyde was synthesized for the detoxification of hazardous metal ions. The resin was characterized by Fourier transform infrared, ¹H, and ¹³C nuclear magnetic resonance spectroscopy, and its morphology was established through scanning electron microscope and X‐ray diffraction. The resin was analyzed by thermogravimetric analysis to assess the thermal stability, in which the resin could be used in high temperature aqueous solutions for the elimination of harmful metal ions. The ion‐exchange property of the resin was evaluated by batch technique for specific metal ions viz. Fe³⁺, Co²⁺, Ni²⁺, Cu²⁺, Zn²⁺, and Pb²⁺. The study was extended to three variations such as effect of metal ion uptake in the presence of various electrolytes in different concentrations, effect of pH, and effect of contact time. The outcome proved that the resin can be used as a strong cation‐exchanger to remove various metal ions from the solutions. The resin could be regenerated and reused with quantitative recovery of metal ions for few cycles. On comparison with the earlier reported resins, the synthesized resin has found excellent capability of metal ion recovery. The resin possesses an utmost ion‐exchange capacity, which is in good harmony with isotherm models and kinetics. Copyright © 2015 John Wiley & Sons, Ltd.     

Bio‐inspired method to fabricate poly‐dopamine/reduced graphene oxide composite membranes for dyes and heavy metal ion removal

Due to the narrow layer spacing, graphene oxide (GO) composite membrane usually exhibits a relatively low water flux in the process of wastewater treatment. In this study, GO was reduced to reduced graphene oxide through a bio‐inspired method, which was functionalized modified by poly‐dopamine (PDA). Then a series of PDA/reduced graphene oxide sheet films were prepared by vacuum filtration on the surface of cellulose acetate membrane (under the pressure of −0.1 MPa). The result indicated that the novel membranes had an excellent stability owing to the cross‐link of PDA. In addition, the hydrophilicity of membrane was increased significantly after PDA modification, which presented a superior water flux than pure GO composite membrane. More importantly, as‐prepared membranes were successfully applied for the removal of dyes (including Congo red, methylene blue, and rhodamine B) and heavy mental ion (Cu(II)) from simulated wastewater. This work might provide a new method for preparation and application of GO composite membranes.     

Preparation of PSSS‐grafted polysulfone microfiltration membrane and its rejection and removal properties towards heavy metal ions

3‐Hydroxy‐N,N‐diethylaniline (HDEA) as a tertiary aromatic amine was introduced onto the surface of chloromethylated polysulfone (CMPSF) microfiltration membrane through modification reaction, resulting in the modified membrane PSF‐DEA. A redox surface‐initiating system (DEA/APS) was constituted by the bonded tertiary aromatic amine group DEA and ammonium persulfate (APS) in aqueous solution, and so, the free radicals formed on the membrane initiated sodium p‐styrenesulfonate (SSS) as an anionic monomer to produce graft polymerization, getting the grafting‐type composite microfiltration membrane, PSF‐g‐PSSS membrane. Subsequently, the adsorption property of PSF‐g‐PSSS membrane for three heavy metal ions, Pb²⁺, Zn²⁺, and Hg²⁺ ions, was fully examined, and the rejection performance of PSF‐g‐PSSS membrane towards the three heavy metal ions was emphatically evaluated via permeation experiments. The experimental results show that by the initiating of the surface‐initiating system of DEA/APS, the graft polymerization can smoothly be carried out under mild conditions. PSF‐g‐PSSS membrane as a functional microfiltration membrane has strong adsorption ability for heavy metal ions by right of strong electrostatic interaction (or ion exchange action) between the anionic sulfonate ions on the membrane and heavy metal ions. The order of adsorption capacity is Pb²⁺ > Zn²⁺ > Hg²⁺, and the adsorption capacity of Pb²⁺ ion gets up to 2.18 μmol/cm². As the volume of permeation solutions, in which the concentrations of the three metal ions are 0.2 mmol/L, are in a range of 50 to 70 mL, the rejection rate of PSF‐g‐PSSS membrane for the three heavy metal ions can reach a level of 95%, displaying a fine rejection and removing performance towards heavy metal ions.     

Poly(butyl methacrylate)-grafted alginate/Fe3O4 nanocomposite: Synthesis and its application for removal of dyes

This study involved the utilization of a free radical-graft copolymerization reaction for the development of a novel adsorbent, namely, poly(butyl methacrylate)-grafted alginate/Fe₃O₄ nanocomposite (PBMA-gft-Alg/Fe₃O₄). Transmission electron microscopy, scanning electron microscopy, energy-dispersive X-ray analysis, X-ray diffraction patterns analysis, and Fourier transform infrared spectroscopy (FT-IR) were carried out for the characterization of Fe₃O₄ NPs and PBMA-gft-Alg/Fe₃O₄ nanocomposites. The capability of nanocomposites and nanoparticles to adsorb dyes such as MG and MB, resulting in their removal from aqueous media, was evaluated under different conditions such as pH, temperature, contact time, and dose of adsorbent. Optimum parameters for adsorption of dyes were found to be pH of 10, 50°C, contact time of 180 min, and 0.2 g of adsorbent. Efficiency of the PBMA-gft-Alg/Fe₃O₄ nanocomposite was found to be significantly greater than that of Fe₃O₄ NPs for eliminating the desired dye. Langmuir, Freundlich, Sips, and Temkin models were used for testing the experimental data. Freundlich model was the one that best described the adsorption.     

Study on the thin-film composite nanofiltration membrane for the removal of sulfate from concentrated salt aqueous: Preparation and performance

Thin-film composite (TFC) nanofiltration (NF) membrane was prepared through the interfacial polymerization between piperazine (PIP) and trimesoyl chloride (TMC) on the polysulphone support membrane. The chemical structure of membrane surface was studied by attenuated total reflectance infrared (ATR-IR) and X-ray photoelectronic spectroscopy (XPS). Parametric studies were conducted by varying reaction time, curing temperature, curing time and additives in PIP solution for obtaining the optimum polymerization conditions. Systematic performance studies were conducted with different feed solutions, feed concentrations, feed pHs, operating temperatures and pressures. Continuous and comparative tests were also conducted to determine the performance stability and separation efficiency of the thin-film composite NF membrane prepared. High performance thin-film composite NF membrane for the selective sulfate removal from concentrated sodium chloride aqueous with the water permeability coefficient of 75 L/(m² h MPa) could be prepared under specific conditions. Experimental results on concentrated mixed solution of NaCl and Na₂SO₄ demonstrated that the NF membrane developed could be successfully used for the removal of sodium sulfate from the concentrated brine of chloralkali industry with high permeate flux, selectivity and performance stability.     

Polyphenylsulfone/multiwalled carbon nanotubes mixed ultrafiltration membranes: Fabrication,characterization and removal of heavy metals Pb2+, Hg2+, and Cd2+ from aqueous solutions

Polyphenylsulfone/multiwalled carbon nanotubes/polyvinylpyrrolidone/1-methyl-2-pyrrolidone mixed matrix ultrafiltration flat-sheet membranes were fabricated via phase inversion process to inspect the heavy metals separation efficacy from aqueous media. Fabricated membranes cross-sectional morphological changes and the topographical alterations were assessed with Scanning electron microscopy (SEM) and atomic force microscopy (AFM). Particularly, MWCNTs assisted membranes exhibited better permeability ability as well as heavy metal removal enactment than virgin membrane. The dead-end filter unit was engaged in current research to examine the permeability and heavy metal removal competence of membranes. With the continuous enhancement of MWCNTs wt% in a polymer matrix, significant enhancement was observed with pure water flux study, from 41.69 L/m² h to >185 L/m² h as well as with the heavy metals separation study. Added additive MWCNTs can impact the pore sizes in membranes. The heavy metal separation results achieved, the membrane with 0.3 wt% of MWCNTs (PCNT-3) exhibited >98%, >76% and >72% for Pb²⁺, Hg²⁺ and Cd²⁺ ions, respectively. Overall, MWCNTs introduced PPSU membranes exposed best outcomes with heavy metals contained wastewater treatment.     

Formation of appropriate sites on nanofiltration membrane surface for binding TiO2 photo-catalyst: Performance, characterization and fouling-resistant capability

Titanium dioxide (TiO₂) nanoparticles were assembled on the surface of nanofiltration blend membrane. For settling TiO₂ on the membrane surface, two membrane categories were used: (i) unmodified polyethersulfone (PES)/polyimide (PI) blend membrane, and (ii) –OH functionalized PES/PI blend membrane with different concentrations of diethanolamine (DEA). These membranes were radiated by UV light after TiO₂ depositing with different concentrations. 15 min immersion in colloidal suspension and 15 min UV irradiation with 160 W lamps were used for modification. The modification resulted in the formation of a photo-catalytic property with enhanced membrane hydrophilicity. The self-assembly of TiO₂ nanoparticles was established through coordinance bonds with –OH functional groups on the membrane surface. A comparison between the UV irradiated TiO₂ deposited blend membrane and deposited-functionalized blend membranes showed that –OH groups originate excellent adhesion of TiO₂ nanoparticles on the membrane surface, increase reversible deposition, and diminish irreversible fouling. The membranes were characterized using SEM, FTIR, EDX, contact angle, cross flow filtration, and antifouling measurements. SEM images show that the presence of –OH groups on the DEA-modified membrane surface is the main parameter for extra uniformly settlement of TiO₂ nanoparticles on the membrane surface. This procedure is a superior technique for modification of PES/PI nanofiltration membranes to enhance water flux and minimization membrane fouling.     

A quantum mechanics/molecular mechanics (QM/MM) investigation on the mechanism of adsorptive removal of heavy metal ions by lignin: single and competitive ion adsorption

In this paper, an adsorption removal mechanism of heavy metal ions (Pb, Cu, Cd, Zn, and Ni) by lignin is investigated by molecular and quantum chemical modeling. First, the lowest energy sites of lignin for heavy metal ions were investigated using a Metropolis Monte Carlo search and simulated annealing. Then, equilibrium adsorption capacities of lignin for heavy metal ions were calculated with conductor-like screening models with a segmented activity coefficients, together with generalized gradient approximation and Volsko–Wilk–Nusair density functional functional theory. These calculations followed the local pseudo-thermodynamic equilibrium at the interface of lignin and ion-containing effluent. Several kinetic Monte Carlo simulations were performed to analyze the surface kinetics of ion adsorption. The affinity of lignin for metal ions follows the order: Pb > Cu > Cd > Zn > Ni which is in agreement with experimental observations. The stability of ions follows the order: Pb > Cd > Zn > Ni > Cu, indicating that the adsorption affinity does not demand the same order of stability on ions. In addition, it was found that while the adsorption of heavy metal ions on the lignin is accessible, the adsorbed heavy metal ions, however, are less stable than the adsorbed water molecules. As such, the used lignin must be replaced by fresh lignin in a cyclic manner. While lignin provides desirable adsorption performance for single ion removal, it failed in processing of practical heavy metal ion solutions expected in environmental issues.     

Efficient removal of heavy metal ions using hydrophilic thiacalix[4]arene doped polyaniline prepared by emulsion polymerization: conductivity,isotherm and kinetic study

The adsorption capacity of conductive polyaniline doped by thiacalix[4]arene tetrasulfonate (PANI–TCAS) towards Cu(II), Cd(II), Co(II) and Cr(III) was investigated through batch adsorption techniques, and the extent of adsorption was measured as a function of pH, initial metal ion concentration and contact time. It was found that the metal ion removal reached maximum at pH 8.0 and remained constant after 60 min. Experimental data was fitted to Langmuir, Freundlich, Redlich–Peterson and Temkin equation models with the maximum adsorption capacity calculated to be 833.3, 555.5, 526.3 and 500 for Cr³⁺, Cu²⁺, Co²⁺ and Cd²⁺, respectively, from the Langmuir isotherm model. The kinetic study was carried out through pseudo‐first‐order, pseudo‐second‐order, Elovich kinetic and intraparticle diffusion models in which the related correlation coefficient for each kinetic model showed that the pseudo‐second‐order rate equation was better described by the adsorption process. XRD spectra, SEM and TEM images of the adsorbent revealed a homogeneous distribution of nano‐sized particle structure with a porous surface, the morphology of which brings about high adsorption capacity for the PANI–TCAS molecular nanocomposite which in turn was observed by the AFM micrograph. The conductivity of thiacalix[4]arene tetrasulfonate doped polyaniline after metal ion adsorption was also assessed, and the four‐probe measurement technique revealed conductivity increment as high as 102.4 S cm^?1 with a 100 order of magnitude enhancement. Copyright © 2015 John Wiley & Sons, Ltd.     

Insight into the performance of novel kaolinite-cellulose/cobalt oxide nanocomposite as green adsorbent for liquid phase abatement of heavy metal ions: Modelling and mechanism

A cost-efficient kaolinite-cellulose/cobalt oxide green nanocomposite (Kao-Cel/Co₃O₄ NC) was successfully synthesized, and utilized as a promising material for removing Pb²⁺ and Cd²⁺ from aqueous solution. The fabricated nanocomposite has been characterized by Fourier transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy-energy dispersive X-ray, high-resolution transmission electron microscopy, and Brunauer-Emmett-Teller analysis. The batch methodology was exploited for optimization of process parameters and the optimized conditions were found to be adsorbent dosage (2.0 g/L), extraction time (50 min), initial concentration (60 mg/L), and initial solution pH (6). Kao-Cel/Co₃O₄ NC displayed excellent adsorption properties and achieved maximum saturation capacity (Q_m) of 293.68 mg Pb²⁺/g and 267.85 mg Cd²⁺/g, with an equilibration time of 50 min at 323 K. The Langmuir model best expressed the isotherm data recommending the adsorption onto energetically homogeneous NC surface, while the compatibility of kinetics data with pseudo-second-order model revealed the dependency of adsorption rate on adsorption capacity, and probable involvement of chemisorption in the rate-controlling step. Electrostatic interaction and ion exchange mechanism were responsible for the uptake of Pb²⁺ and Cd²⁺ by Kao-Cel/Co₃O₄ NC as demonstrated by Fourier transform infrared spectroscopy and pH studies. Thermodynamic parameters confirmed the physical, spontaneous, and endothermic sequestration processes. Real water investigation specified that the present adsorbent could be effectively used for liquid phase decontamination of Pb²⁺ and Cd²⁺. The nanocomposite exhibited high reusability, which could be utilized efficiently for five runs with sustainable results. In summary, this study portrayed the present nanocomposite as an emerging material for the adsorption of heavy metal ions particularly Pb²⁺ and Cd²⁺.     

Preparation of poly(vinylalcohol)/poly(acrylamide‐co‐vinyl imidazole)/γ‐Fe2O3 semi‐IPN nanocomposite and their application for removal of heavy metal ions from water

A series of magnetic semi‐interpenetrating polymer network (semi‐IPN) hydrogels was prepared in one‐stage strategy composed of linear poly(vinyl alcohol) (PVA) chains and magnetic γ‐Fe₂O₃ nanoparticles entrapped within the cross‐linked poly(acrylamide‐co‐vinylimidazole) (poly(AAm‐co‐VI)) network. The influence of PVA, weight ratio of AAm:VI, γ‐Fe₂O₃, and MBA on the swelling properties of the obtained nanocomposite hydrogels was evaluated. The prepared magnetic semi‐IPN hydrogels were fully characterized and used as absorbent for removal of Pb(II) and Cd(II) from water. Factors that influence the metal ion adsorption such as solution pH, contact time, initial metal ion concentration, and temperature were studied in details. The experimental results were reliably described by Langmuir adsorption isotherms. The adsorption capacity of semi‐IPN nanocomposite for Pb(II) and Cd(II) were175.80 and 149.76 mg g^?1, respectively. The kinetic experimental data indicated that the chemical sorption is the rate‐determining step. According to thermodynamic studies, Pb(II) and Cd(II) adsorption on the hydrogels was endothermic and also chemical in nature. The prepared magnetic PVA/poly(AAm‐co‐VI) semi‐IPN hydrogels could be employed as efficient and low‐cost adsorbents of heavy metal ions from water. Copyright © 2016 John Wiley & Sons, Ltd.     

The generalized hybrid orbital method for combined quantum mechanical/molecular mechanical calculations: formulation and tests of the analytical derivatives

 Hybrid quantum mechanical (QM) and molecular mechanical (MM) potentials are becoming increasingly important for studying condensed-phase systems but one of the outstanding problems in the field has been how to treat covalent bonds between atoms of the QM and MM regions. Recently, we presented a generalized hybrid orbital (GHO) method that was designed to tackle this problem for hybrid potentials using semiempirical QM methods [Gao et al. (1998) J Phys Chem A 102: 4714–4721]. We tested the method on some small molecules and showed that it performed well when compared to the purely QM or MM potentials. In this article, we describe the formalism for the determination of the GHO energy derivatives and then present the results of more tests aimed at validating the model. These tests, involving the calculation of the proton affinities of some model compounds and a molecular dynamics simulation of a protein, indicate that the GHO method will prove useful for the application of hybrid potentials to solution-phase macromolecular systems. Received: 4 October 1999 / Accepted: 18 December 1999 / Published online: 5 June 2000     

Synergistic effects of nano-ZnO/multi-walled carbon nanotubes/chitosan nanocomposite membrane for the sensitive detection of sequence-specific of PAT gene and PCR amplification of NOS gene

The remarkable synergistic effects of the zinc oxide (ZnO) nanoparticles and multi-walled carbon nanotubes (MWNTs) were developed for the ssDNA probe immobilization and fabrication of the electrochemical DNA biosensor. The ZnO/MWNTs/chitosan nanocomposite membrane-modified glassy carbon electrode (ZnO/MWNTs/CHIT/GCE) was fabricated and the ssDNA probes were immobilized on the modified electrode surface. The preparation method is quite simple and inexpensive. The hybridization events were monitored by differential pulse voltammetry (DPV) using methylene blue (MB) as an indicator. As compared with previous MWNTs-based DNA biosensors, this composite matrix combined the attractive biocompatibility of ZnO nanoparticles with the excellent electron-transfer ability of MWNTs and fine membrane-forming ability of CHIT increased the DNA attachment quantity and complementary DNA detection sensitivity. The approach described here can effectively discriminate complementary DNA sequence, noncomplementary sequence, single-base mismatched sequence and double-base mismatched sequence related to phosphinothricin acetyltransferase (PAT) gene in transgenic corn. Under optimal conditions, the dynamic detection range of the sensor to PAT gene complementary target sequence was from 1.0 × 10⁻¹¹ to 1.0 × 10⁻⁶ mol/L with the detection limit of 2.8 × 10⁻¹² mol/L. The polymerase chain reaction (PCR) amplification of nopaline synthase (NOS) gene from the real sample of one kind of transgenic soybeans was also satisfactorily detected with this electrochemical DNA biosensor, suggesting that the ZnO/MWNTs/CHIT nanocomposite hold great promises for sensitive electrochemical biosensor applications.     

A new,validated HPLC‐MS/MS method for the simultaneous determination of the anti‐cancer agent capecitabine and its metabolites: 5′‐deoxy‐5‐fluorocytidine, 5′‐deoxy‐5‐fluorouridine, 5‐fluorouracil and 5‐fluorodihydrouracil,in human plasma

A rapid and selective liquid chromatography/tandem mass spectrometric method was developed for the simultaneous determination of capecitabine and its metabolites 5′‐deoxy‐5‐fluorocytidine (5′‐DFCR), 5′‐deoxy‐5‐fluorouracil (5′‐DFUR), 5‐fluorouracil (5‐FU) and dihydro‐5‐fluorouracil (FUH₂) in human plasma. A 200 μL human plasma aliquot was spiked with a mixture of internal standards fludarabine and 5‐chlorouracil. A single‐step protein precipitation method was employed using 10% (v/v) trichloroacetic acid in water to separate analytes from bio‐matrices. Volumes of 20 μL of the supernatant were directly injected onto the HPLC system. Separation was achieved on a 30 × 2.1 mm Hypercarb (porous graphitic carbon) column using a gradient by mixing 10 mm ammonium acetate and acetonitrile–2‐propanol–tetrahydrofuran (1 : 3 : 2.25, v/v/v). The detection was performed using a Finnigan TSQ Quantum Ultra equipped with the electrospray ion source operated in positive and negative mode. The assay quantifies a range from 10 to 1000 ng/mL for capecitabine, from 10 to 5000 ng/mL for 5′‐DFCR and 5′‐DFUR, and from 50 to 5000 ng/mL for 5‐FU and FUH₂ using a plasma sample of 200 μL. Correlation coefficients (r²) of the calibration curves in human plasma were better than 0.99 for all compounds. At all concentration levels, deviations of measured concentrations from nominal concentration were between ?4.41 and 3.65% with CV values less than 12.0% for capecitabine, between ?7.00 and 6.59% with CV values less than 13.0 for 5′‐DFUR, between ?3.25 and 4.11% with CV values less than 9.34% for 5′‐DFCR, between ?5.54 and 5.91% with CV values less than 9.69% for 5‐FU and between ?4.26 and 6.86% with CV values less than 14.9% for FUH₂. The described method was successfully applied for the evaluation of the pharmacokinetic profile of capecitabine and its metabolites in plasma of treated cancer patients. Copyright © 2009 John Wiley & Sons, Ltd.