Method development and validation of LC-MS/MS-based assay for the simultaneous quantitation of trastuzumab and pertuzumab in cynomolgus monkey serum and its application in pharmacokinetic study.

We present a simple and robust LC-MS/MS assay for the simultaneous quantitation of an antibody cocktail of trastuzumab and pertuzumab in monkey serum. The LC-MS/MS method saved costs, decreased the analysis time, and reduced quantitative times relative to the traditional ligand-binding assays. The serum samples were digested with trypsin at 50°C for 60 min after methanol precipitation, ammonium bicarbonate denaturation, dithiothreitol reduction, and iodoacetamide alkylation. The tryptic peptides were chromatographically separated using a C18 column (2.1 × 50 mm, 2.6 µm) with mobile phases of 0.1% formic acid in water and acetonitrile. The other monoclonal antibody, infliximab, was used as internal standards to minimize the variability during sample processing and detection. A unique peptide for each monoclonal antibody was simultaneously quantified using LC-MS/MS in the multiple reaction monitoring mode. Calibration curves were linear from 2.0 to 400 µg/mL. The intra- and inter-assay precision (%CV) was within 8.9 and 7.4% (except 10.4 and 15.1% for lower limit of quantitation), respectively, and the accuracy (%Dev) was within ±13.1%. The other validation parameters were evaluated, and all results met the acceptance criteria of the international guiding principles. Finally, the method was successfully applied to a pharmacokinetics study after a single-dose intravenous drip administration to cynomolgus monkeys.

Simultaneous quantitative determination of liraglutide and insulin degludec in rat plasma by liquid chromatography-tandem mass spectrometry method and its application.

A simple, fast and high-throughput LC-tandem mass spectrometry method was developed and validated to simultaneously measure liraglutide and insulin degludec in rat plasma. After protein precipitation, plasma samples were subjected to gradient elution using an InertSustain Bio C18 column with 1000/20/1 water/acetonitrile/formic acid (v/v/v) and 1000/1 acetonitrile/formic acid (v/v) as the mobile phase. The method was validated from 1.00 to 500 ng/mL of liraglutide and insulin degludec. Further, the extraction recovery from the plasma was 41.8%-49.2% for liraglutide and 56.5%-69.7% for insulin degludec. Intra- and inter-day precision of liraglutide was 3.5%-9.4% and 8.4%-9.8%, respectively, whereas its accuracy was between -12.6% and -1.3%. Intra- and inter-day precision of insulin degludec was 5.2%-13.6% and 11.8%-19.1%, respectively, showing an accuracy between -3.0% and 9.9%. As a result, the method was successfully applied to a pharmacokinetics study of liraglutide and insulin degludec following a single-dose subcutaneous administration to rats.

Factors influencing the photocatalytic activity of rutile TiO2 nanorods with different aspect ratios for dye degradation and Cr(VI) photoreduction.

Shape-controlled rutile TiO2 nanorods (NRs) with large {110} and small {111} exposed facets were prepared by hydrothermal treatment of a peroxo titanic acid (PTA) solution. The aspect ratio of the NRs was controlled by the pH of the PTA solution and the addition of polyvinyl alcohol (PVA) or polyvinyl pyrrolidone (PVP). The spatial separation of reduction and oxidation sites, where {110} facets act as reduction sites and {111} facets as oxidation ones, was revealed by tracking the distribution of Pt and PbO2 deposited on the NR surfaces. The MB degradation activity depended on the aspect ratio of the rutile NRs because of the different separation efficiencies of photo-generated carriers on different facets. Meanwhile, the Cr(VI) reduction activity was governed by the slight shift of the conduction-band potential of the rutile NRs estimated from Mott-Schottky plots, which may be caused by the variation of the content of {110} facets in the rutile NRs. Among the prepared rutile NRs, the sample prepared using a PTA solution at pH 4 containing 10 mg of PVA showed higher activity for photocatalytic Cr(VI) reduction than Degussa P25. These results provide a feasible method to design efficient TiO2 photocatalysts with tunable photoreactivity for environmental applications.

Synthesis of novel CeO2-BiVO4/FAC composites with enhanced visible-light photocatalytic properties.

To utilize visible light more effectively in photocatalytic reactions, a fly ash cenosphere (FAC)-supported CeO2-BiVO4 (CeO2-BiVO4/FAC) composite photocatalyst was prepared by modified metalorganic decomposition and impregnation methods. The physical and photophysical properties of the composite have been characterized by X-ray diffraction (XRD), scanning electron microscope (SEM) and energy dispersive X-ray spectroscopy (EDX), X-ray photoelectron spectroscopy (XPS), and UV-Visible diffuse reflectance spectra. The XRD patterns exhibited characteristic diffraction peaks of both BiVO4 and CeO2 crystalline phases. The XPS results showed that Ce was present as both Ce(4+) and Ce(3+) oxidation states in CeO2 and dispersed on the surface of BiVO4 to constitute a p-n heterojunction composite. The absorption threshold of the CeO2-BiVO4/FAC composite shifted to a longer wavelength in the UV-Vis absorption spectrum compared to the pure CeO2 and pure BiVO4. The composites exhibited enhanced photocatalytic activity for Methylene Blue (MB) degradation under visible light irradiation. It was found that the 7.5wt.% CeO2-BiVO4/FAC composite showed the highest photocatalytic activity for MB dye wastewater treatment.

Effects of decabromodiphenyl ether (BDE-209) on the avoidance response, survival, growth and reproduction of earthworms (Eisenia fetida).

The effects of decabromodiphenyl ether (BDE-209) on avoidance response, survival, growth, and reproduction of earthworms (Eisenia fetida) were investigated under laboratory conditions using natural and artificial soils as substrate. Results showed that no significant avoidance response was observed when earthworms were exposed to 0.1-1000 mg/kg of BDE-209 for 48 h. After 28-days exposure, no significant effects on survival and growth of adult earthworms was induced by 0.1-1000 mg/kg of BDE-209 indicating the Lowest Observed Effect Level (LOEL) of BDE-209 on their survival and body weight was more than 1000 mg/kg. Except for a significant decrease in the number of juveniles per hatched cocoon in artificial soils at 1000 mg/kg of BDE-209, no significant effects on reproductive parameters (e.g. cocoon production per earthworms, weight per cocoon and cocoon hatchability) were observed. These results suggest that adult earthworms have a strong tolerance for BDE-209 exposure in soils, but a potential toxicity does exist for earthworm embryos or juveniles.

Comparison of two adsorbents for the removal of pentavalent arsenic from aqueous solutions.

Two adsorbents, magnesia-loaded fly ash cenospheres (MGLC) and manganese-loaded fly ash cenospheres (MNLC), were prepared by wet impregnation of fly ash cenospheres with MgCl(2) solution or a mixed solution of MnCl(2) and KMnO(4), respectively. Their physicochemical properties were characterized by scanning electron microscopy, X-ray diffractometry, X-ray fluorescence spectrometry, and Fourier transform infrared spectrometry. Sorption experiments were conducted to examine the effects of adsorbent dosage, pH, time, temperature, ionic strength and competing anions on As(V) removal by MGLC and MNLC. Both MGLC and MNLC had greater pH buffering capacity and were less affected by changes in ionic strength. Competing anions (carbonate and dihydric phosphate) had a larger impact on As(V) removal by MNLC than by MGLC. Adsorption on MNLC reached equilibrium at 60 min, while adsorption on MGLC reached equilibrium at 120 min. The Langmuir adsorption isotherm was a good fit for the experimental data of As(V) adsorption on MGLC and MNLC, and the adsorption kinetics for both followed the pseudo-second-order rate equation. MGLC and MNLC had a larger removal capacity for As(V) than the cenospheres. Compared with MNLC, MGLC is a better absorbent.

Feasibility of manufacturing geopolymer bricks using circulating fluidized bed combustion bottom ash.

This paper presents a study on geopolymer bricks manufactured using bottom ash from circulating fluidized bed combustion (CFBC). The alkali activators used for synthesis were sodium silicate, sodium hydroxide, and potassium hydroxide and lithium hydroxide solutions. The study included the impact of alkali activator on compressive strength. The reaction products were analysed by XRD, FT-IR and SEM/EDS. The compressive strength of bricks was dependent on the modulus of the sodium silicate activator and the type and concentration of alkali activator. The highest compressive strength could be gained when the modulus was 1.5, and the value could reach 16.1 MPa (7 d after manufacture) and 21.9 MPa (28 d after manufacture). Under pure alkaline systems, the compressive strength was in the order of 10 M KOH > 10 M NaOH > 5 M LiOH > 5 M KOH > 5 M NaOH. Quartz was the only crystalline phase in the original bottom ash, and no new crystalline phase was found after the reaction. The main product of reaction was amorphous alkali aluminosilicate gel and a small amount of crystalline phase was also found by SEM.

Preparation and adsorption performance of MnO2/PAC composite towards aqueous glyphosate.

Glyphosate (N-phosphonomethylglycine (PMG)) is the organophosphate herbicide most widely used in the world, and industrial production of PMG generates large quantities of wastewater. A manganese dioxide-coated powdered activated carbon (MnO2/PAC) composite was synthesized and investigated for the adsorption of PMG from wastewater. The results of scanning electron microscopy (SEM) combined with energy-dispersive X-ray spectrometry (EDAX) revealed that MnO2 was formed on the surface of the carbon during the modification process. Batch adsorption results showed that the optimal pH for glyphosate adsorption on MnO2/PAC was 3.0. In the range 0.01(-1) molL(-1), glyphosate removal by MnO2/PAC decreased with an increase in ionic strength. Among the coexistent anions, only phosphate showed significant inhibition of PMG removal due to competitive complexation. Batch studies revealed that MnO2/PAC could reach a maximum PMG adsorption capacity of 283 mg g(-1). The Langmuir equilibrium model was found to be suitable for describing PMG sorption, and kinetic studies revealed that adsorption followed second-order rate kinetics. It was also proved that the adsorbed PMG could be effectively desorbed from MnO2/PAC in 1.0 molL(-1) NaOH. All of these results implied that the MnO2/PAC composite may be used as an effective adsorbent for recycling PMG from wastewater.

Reactive sorption of mercury(II) on to poly(m-phenylenediamine) microparticles.

Poly(m-phenylenediamine) (PmPD) microparticles, from the monomer with two amino groups, were synthesized through chemical oxidation, and the strong adsorbability of mercury ions on to PmPD was systematically examined. The results revealed a rapid adsorption process with an equilibrium time of 30 minutes. Also, the adsorption behaviour showed that the adsorption kinetics was in good agreement with the pseudo-second-order equation. The maximum uptake capacity for mercury (Q(max)) reached approximately 955 mg g(-1) at 0.02 M NaNO3 and 25 degrees C, which decreased appreciably with the increasing of salt concentration. The amount of mercury sorbed at equilibrium steadily increased as the temperature rose from 25 to 45 degrees C, which can be indicative of an endothermic process. The pH value of the solution seemed to exhibit little influence on the adsorption capacity. The adsorption mechanisms, including Hg2+ complexation with nitrogen and ion exchange between Hg2+ and H+ on PmPD chains, are proposed on the basis of Fourier transform infrared (FTIR) and X-ray photoelectron spectroscopy (XPS) analysis.

Column-mode fluoride removal from aqueous solution by magnesia-loaded fly ash cenospheres.

Column experiments in a fixed bed reactor packed with a certain amount of magnesia-loaded fly ash cenospheres (MLC) were conducted to examine the effects of adsorbent mass, flow velocities, influent concentrations and coexisting anions on fluoride removal. The breakthrough time increased with an increase in adsorbent mass, but decreased with increasing influent fluoride concentration. The exhaustion time decreased with the increase in the influent fluoride concentration. The capacity at the breakthrough point increased with an increase in adsorbent mass, flow velocity and the influent fluoride concentration. The capacity at the exhaustion point increased with an increase in flow velocity, but showed no specific trend with an increase in the initial fluoride concentration. The bed volumes at breakthrough point increased with an increase in adsorbent mass, flow velocity and the influent fluoride concentration. The empty bed contact time decreased with an increase in flow velocity. The coexisting anions reduced the adsorption capacity of the fixed bed reactor in the order: mixture of all three anions > dihydric phosphate > nitrate > sulfate. The adsorbent exhaustion rate decreased with the increase in flow velocity and adsorbent mass, whereas it increased with increasing influent fluoride concentration. Columns with large amounts of MLC are preferable in order to obtain optimal results during the adsorption process, and the higher the flow velocity, the better the column performance. The Bohart and Adams model and the Thomas model were applied to the experimental results. Column adsorption was reversible and the regeneration operation was accomplished by pumping 0.2 M NaOH through the loaded MLC column.

Kinetic studies of adsorption of Pb(II), Cr(III) and Cu(II) from aqueous solution by sawdust and modified peanut husk.

Sawdust and modified peanut husk were used as adsorbents to remove Pb(II), Cr(III) and Cu(II) from aqueous solution. Results of kinetic experiments demonstrated that the adsorption was effective and rapid. Three different kinds of kinetic models (i.e., intraparticular diffusion model, Lagergren-first-order and second-order equations) were used to investigate the adsorption mechanisms. The adsorption of heavy metals on sawdust and modified peanut husk is not an intraparticular diffusion control. The kinetic adsorption data can be described by the second-order equation and the adsorption might be a rate-limiting control. The suitability of the adsorbent was tested by fitting the adsorption data with Langmuir and Freundlich isotherms, which gave good fits with both isotherms.

Synthesis of buoyant metal-coated fly ash cenosphere and its excellent catalytic performance in dye degradation.

In this work, Ag(+) and Ag(0) were absorbed onto the surface of 3-mercaptopropyltriethoxysilane modified fly ash cenospheres (FACs) in two Ag activation processes. The activation methods, avoiding traditional surface sensitization by SnCl2, successfully initiated electroless copper particles deposition for the preparation of buoyant Cu-FAC and CuAg-FAC composites. The CuAg-FAC had a much more uniform morphology than the Cu-FAC. The catalytic performance of the Cu-FAC and CuAg-FAC was examined by the reduction of Orange IV azo dye with the presence of NaBH4. 98.4% of Orange IV was rapidly reduced within 25 min by the CuAg-FAC, whereas 76.4% of Orange IV was removed by the Cu-FAC. The results reveal that the degradation processes matched well with the pseudo-first-order kinetics model, and rate constants of 0.057 and 0.186 min(-1) were obtained for the Cu-FAC and CuAg-FAC, respectively. Moreover, two other dyes of Orange II and Reactive Black 5 were also efficiently reduced by the CuAg-FAC which could be easily recycled and stably reused at least four times. These buoyant metal-coated FAC composites would be very useful in various catalytic reductions.

Electrocatalytic reduction of bromate based on Pd nanoparticles uniformly anchored on polyaniline/SBA-15.

A nano-composite electrocatalyst of Pd nanoparticles (Pd-NPs) anchored on polyaniline (PANI) supported by mesoporous SBA-15 (Pd-NPs/PANI/SBA-15), was synthesized using an in situ chemical method. Transmission electron microscopy showed that the Pd-NPs were homogeneously dispersed. Fourier-transform infrared and X-ray photoelectron spectroscopies confirmed that the Pd-NPs in the metallic state (Pd(0)) were predominantly immobilized on nitrogen sites in the PANI chains. The electrochemical performance of Pd-NPs/PANI/SBA-15 for electrocatalytic reduction of bromate (BrO3(-)) in an acidic medium was investigated by cyclic voltammetry (CV) and amperometric measurement. The reduction peak in the CV curves in the region 0.12 to -0.22V (vs. SCE) corresponded to response of BrO3(-) electroreduction, and the reduction peak current was well fitted linearly to the BrO3(-) concentration. It is proposed that the bromate ions diffuse to the Pd-NPs active sites and then the electrocatalytic reduction occurred with the H(+) doped in PANI. Furthermore, by amperometric measurement, Pd-NPs/PANI/SBA-15 showed relatively high sensitivity with respect to BrO3(-) concentration in the range of 8µmolL(-1) to 40mmolL(-1). Continuous CV for 200 cycles proved that Pd-NPs/PANI/SBA-15 had excellent electrocatalytic stability. These results show that Pd-NPs/PANI/SBA-15 is effective for electrocatalytic reduction of BrO3(-) and has great potential for the fabrication of BrO3(-) electrochemical sensor.

The role of temperature on Cr(VI) formation and reduction during heating of chromium-containing sludge in the presence of CaO.

In this study, the temperature dependence of Cr(VI) formation and reduction in the presence of CaO was examined during the thermal treatment of sludge that contains chromium. thermogravimetry-differential scanning calorimetry and X-ray diffractometry were used to characterize the thermal behavior and phase transformation, respectively. Na2CO3 leaching procedure was employed to determine the amount of Cr(VI). The result showed that CaO promoted Cr(III) oxidation, however, its influence is very dependent on heating temperature, with the extent of the effect varying with temperature. From 200-400 °C, the presence of CaO facilitated formation of intermediate product Cr2O3+x containing Cr(VI) during dehydration of chromium hydrate, while Cr2O3+x would decompose as temperature over 400 °C, accompanied by part of Cr(VI) being reduced to Cr(III). From 500 to 900 °C, Cr(III) reacted with CaO to form a leachable CaCrO4 product. This product was stable and a prolonged heating time did not reduce the amount of Cr(VI) significantly. At 1000-1200 °C, part of CaCrO4 was reduced to Ca(CrO2)2 in 1h. While extended heating time above 1h resulted in the Ca(CrO2)2 being oxidized reversibly to CaCrO4 at 1200 °C. Since CaCrO4 is thermodynamically less stable over 1000 °C, MgO could induce CaCrO4 to be reduced into MgCr2O4 at around 900 °C, lower than that for the reduction from CaCrO4 into Ca(CrO2)2. It suggested that adding MgO might be a potential approach for inhibiting Cr(VI) formation during heating sludge containing chromium.

Surface modification and bioconjugation of FeCo magnetic nanoparticles with proteins.

Magnetic Fe70Co30 nanoparticles with a cubic shape and a mean size of 15±1.5 nm were fabricated using a magnetron-sputtering-based gas phase condensation deposition method. The particles had a high saturation magnetization of 220 emu/g, which is much higher than that of commercially available iron oxide nanoparticles. The FeCo nanoparticles were modified by 3-aminopropyltriethoxy silane and subsequently activated by glutaraldehyde, leading to successful attachment of aldehyde groups onto nanoparticle surfaces. Three proteins, namely streptavidin, PAPP-A antibody and Nectin-4 antibody, were immobilized on glutaraldehyde activated FeCo nanoparticles, and their loading levels were quantitatively evaluated. Our results show that loading capabilities are 95 µg of streptavidin, 128 µg of PAPP-A, and 125 µg of Nectin-4 antibody per milligram of FeCo nanoparticles, and that the three immobilized proteins retain their binding bioactivity. The protein-FeCo conjugates may find valuable applications involving magnetic separation and purification of proteins and cells, and the magnetic detection of biomolecules.

Stabilization of simulated lead sludge with iron sludge via formation of PbFe12O19 by thermal treatment.

This study investigated the feasibility of stabilizing lead sludge by reaction with iron sludge via the formation of PbFe12O19 through a thermal treatment process. Lead hydroxide was used to simulate lead-laden sludge and the sintering procedure was performed by firing a mixture of this simulated sludge together with iron sludge at a Fe/Pb molar ratio of 12 over the temperature range from 650 to 1400 °C. The accompanying phase transformations as well as the surface characteristic of sintered samples were observed by XRD and SEM, while the leaching behavior of the stabilized sludge in an acidic environment was evaluated by a modified Toxicity Characteristic Leaching Procedure (TCLP) test. The results confirmed that PbFe12O19 acts as a stabilization phase for lead, and showed that the formation of a PbFe12O19 phase began at 750 °C with the lead completely incorporated into the PbFe12O19 phase at 1050 °C. Above 1100 °C, the PbFe12O19 phase began to decompose, accompanied by the reappearance of Fe2O3. The volumes of compressed sludge samples were reduced significantly after thermal treatment, with accompanying volume reductions of 40% at 1050 °C. This study compared the leaching of lead from PbO and sintered sludge samples using a prolonged TCLP test, and the data showed that the PbFe12O19 phase was superior to the PbO and that the sintered sludge sample exhibited very high stability under acidic environments. These results suggest a promising and reliable method of reducing lead sludge mobility and toxicity has been identified.

Utilization of nanoparticle labels for signal amplification in ultrasensitive electrochemical affinity biosensors: a review.

Nanoparticles with desirable properties not exhibited by the bulk material can be readily synthesized because of rapid technological developments in the fields of materials science and nanotechnology. In particular their highly attractive electrochemical properties and electrocatalytic activity have facilitated achievement of the high level of signal amplification needed for the development of ultrasensitive electrochemical affinity biosensors for the detection of proteins and DNA. This review article explains the basic principles of nanoparticle based electrochemical biosensors, highlights the recent advances in the development of nanoparticle based signal amplification strategies, and provides a critical assessment of the likely drawbacks associated with each strategy. Finally, future perspectives for achieving advanced signal simplification in nanoparticles based biosensors are considered.

Immobilization of simulated radionuclide 133Cs+ by fly ash-based geopolymer.

The recent nuclear leak in Japan once again attracted people's attention to nuclear safety problems. Because of their poor thermal stability, those low-cost materials such as cement and asphalt cannot be used for the solidification of the radioactive wastes. In this work, the solidification behavior of 133Cs(+) by fly ash-based geopolymer was investigated. Leaching tests (carried out in deionized water, sulfuric acid and magnesium sulfate solutions) revealed that the geopolymer solidification had lower cumulative fraction leaching concentration (CFLC) of 133Cs(+) than that of cemented form. The thermal stability (high-temperature and freeze-thaw resistance) and acid-resistance of the geopolymer were also both better than that of cement. The geopolymer solidification block can acquire a compressive strength up to 30 MPa after 2h calcination at 1000 °C. The morphology and mineral phases of the geopolymer and the geopolymer solidification block were characterized by SEM and XRD, and EDX analysis indicated that most of Cs associated with the amorphous geopolymer gel. These results gave encouragement for the idea that the fly ash-based geopolymer could be used as a low-cost and high-efficiency material for the immobilization of radioactive wastes.

Electrochemical removal of fluoride from water by PAOA-modified carbon felt electrodes in a continuous flow reactor.

A novel poly(aniline-co-o-aminophenol) (PAOA) modified carbon felt electrode reactor was designed and investigated for fluoride removal from aqueous solutions. This reactor design is innovative because it operates under a wider pH range because of coating with a copolymer PAOA ion exchange film. In addition, contaminant mass transfer from bulk solution to the electrode surface is enhanced by the porous carbon felt as an electron-conducting carrier material compared to other reactors. The electrically controlled anion exchange mechanism was investigated by X-ray photoelectron spectroscopy and cyclic voltammetry. The applicability of the reactor in the field was tested through a series of continuous flow experiments. When the flow rate and initial fluoride concentration were increased, the breakthrough curve became sharper, which lead to a decrease in the breakthrough time and the defluoridation capacity of the reactor. The terminal potential values largely influenced fluoride removal by the reactor and the optimal defluoridation efficiency was observed at around 1.2V. The breakthrough capacities were all >10mg/g over a wide pH range (pH 5-9) with an initial fluoride concentration of 10mg/L. Consecutive treatment-regeneration studies over a week (once each day) revealed that the PAOA-modified carbon felt electrode could be effectively regenerated for reuse. The PAOA-modified carbon felt electrode reactor is a promising system that could be made commercially available for fluoride removal from aqueous solutions in field applications.

Defluoridation of water via electrically controlled anion exchange by polyaniline modified electrode reactor.

A polyaniline (PANI) modified electrode reactor was designed for fluoride removal from aqueous solutions. The innovative concept behind the reactor design is that the uptake and elute of fluoride could be well controlled by modulating the potential of the PANI film. The maximum fluoride removal capacity of PANI is more than 20 mg/g at a positive voltage based on the electrically controlled anion-exchange mechanism. The results of batch tests showed that terminal potential values had a major impact on fluoride removal by this PANI, with optimal removal occurring at 1.5 V. The fluoride removal capacity (q(e)) increased rapidly within 5 min and reached equilibrium within 10 min, which indicated a rapid removal velocity of fluoride by PANI under this condition. The applicability of defluoridation using the PANI reactor to treat fluoride-contaminated tap water was also tested through flow cell breakthrough studies. At initial fluoride concentrations of 5 mg/L and 10 mg/L, the breakthrough capacities were 20.08 mg/g and 19.24 mg/g, respectively. Moreover, during the first half of the period before the breakthrough point, the fluoride concentration of the treated solution was below the WHO's recommended levels (1.5 mg/L). The results of the five consecutive treatment-regeneration studies also showed that the PANI films could be reused. Taken together, these results implied that the electrically controlled anion exchange by the PANI-modified electrode reactor may be an effective technique for the removal of fluoride from water.