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• Rh3+ speciation and aquation kinetics depend strongly on the presence of chloride. • UV–vis spectral trends of the Rh3+ complex correlate with electrochemistry. • Rh3+ reduction onset potential determined from cathodic linear sweep voltammograms. • Electrochemical quartz crystal microbalance used to quantify metallic Rh deposition. For back end of line metallization, the wet-chemical deposition of Rh requires investigation as the metal can improve the performance of semiconductor devices, due to its low resistivity and expected favourable electromigration characteristics. This study reports the Rh electrochemistry features in four background electrolytes (KCl, NH 4 Cl, K 2 SO 4 , and (NH 4) 2 SO 4) as well as the stability of Rh3+ in the electrolytes and ultrapure water using UV–vis spectroscopy and it was found that various complexes were formed depending on storage time and mixing time. The onset potentials of the Rh3+ reduction reaction(s) and hydrogen evolution reaction were determined by linear sweep voltammetry. For chloride-based solutions, a much slower stabilization was observed than for sulphate-based solutions, as evidenced by the gradual disappearing of multiple reduction peaks over the course of days. After stabilization, Rh is deposited with a single reduction peak. Although Rh has a high catalytic activity for hydrogen evolution, the adsorption/desorption of hydrogen ions on the metal surface and the onset of Rh3+ reduction occur at well-separated potentials, which allowed us to use an electrochemical quartz crystal microbalance to determine the Rh deposition potential as well as quantify the amount of metal deposited on a Pt-coated electrode. [ABSTRACT FROM AUTHOR]

In the presented work, a study on the solubility and intermolecular interactions of l -serine and L-cysteine was carried out in binary mixtures of H 2 O + dimethylformamide (DMF), H 2 O + dimethylsulfoxide (DMSO), and H 2 O + acetonitrile (ACN) in the temperature range of T = 288.15 K to 308.15 K. l -serine exhibited the highest solubility in water, while L-cysteine was more soluble in water-DMF. The solvation process was assessed through standard Gibbs energy calculations, indicating the solvation stability order: water-ACN > water-DMSO > water-DMF for l -serine, and water-DMF > water-DMSO > water-ACN for L-cysteine. This study also explored the influence of these amino acids on solvent–solvent interactions, revealing changes in chemical entropies and self-association patterns within the binary solvent mixtures. Variation of solubility of L-cysteine in Water-DMF in various mole fraction concentrations of DMF (X DMF) with temperature (K). [Display omitted] • l-serine shows highest solubility in water, generally decreasing with organic components, except water-ACN solvent system. • L-cysteine is more soluble in water-DMF, solubility order: water-DMF > water-DMSO > water-ACN. • Standard Gibbs energy calculations reveal l -serine's stability: most in water-DMSO, least in water-ACN. • Non-covalent interactions govern stability, l -serine's solvation most affected by DMF, while L-cysteine by ACN. [ABSTRACT FROM AUTHOR]

This commentary highlights the significance of the solution stability and preparation of a solution of cocrystal in evaluating anti-tumor activity. It introduces a challenging issue regarding improving the biological activity of an API in cocrystal form. [ABSTRACT FROM AUTHOR]

• Electrodeposition and sodium dithionite reduction for gold recovery was compared. • Gold began to deposit at the potential of lower than −100 mV Hg/HgO. • Cl−, S 2 O 3 2− and SO 3 2− exhibited different effects on gold deposition/reduction. • Sodium dithionite reduction displayed better gold recovery performance. • Sodium dithionite reduction had better solution stability and lower recovery cost. A comparative study was performed on electrodeposition and sodium dithionite reduction for recovering gold in the gold-rich solution from the adsorption of thiosulfate solution by ion exchange resin. Using electrodeposition method, gold started to deposit when the potential was lower than −100 mV Hg/HgO. The rise of Cl− concentration improved gold deposition while the increases of SO 3 2− and S 2 O 3 2− concentrations were unbeneficial to gold deposition. When the solution was deposited at the optimum potential of −600 mV Hg/HgO for 5 h, the gold deposition percentage reached 99.33 %. With sodium dithionite reduction method, the gold reduction percentage achieved 100 % after only 5 min as S 2 O 4 2− dosage was eight times of the theoretical amount. The increases of SO 3 2− and S 2 O 3 2− concentrations hindered gold reduction while the augment of Cl− concentration had no obvious effect. Overall, sodium dithionite reduction method has the advantages of shorter reaction time, higher gold recovery percentage, better solution stability and lower recovery cost, and thus it has a broader industrial application prospect. [ABSTRACT FROM AUTHOR]

The solution speciation of Ga(III) and Fe(III) complexes of two (O,O) donor bearing alkoxycarbonylmethyl-3-hydroxy-2(1 H)-pyridinone ligands was characterized. Moderate stabilities were observed with [ML 3 ] complexes predominating at physiological pH. Significant decomposition of the Ga(III) complexes occurs at low concentration leading to negligible cytotoxic activity in human adenocarcinoma cells. The stoichiometry and stability constants of the gallium(III) and iron(III) complexes of two alkoxycarbonylmethyl-3-hydroxy-2(1 H)-pyridinone ligands were determined by means of pH-potentiometry, UV–Vis spectrophotometry and 1H and 71Ga NMR spectroscopy in aqueous solution. The cytotoxicity of one of the gallium(III) complexes was also measured in multidrug resistant/non-resistant human colon adenocarcinoma cell lines. Iron(III) forms complexes with the studied 3-hydroxy-2-pyridinones of higher stability than gallium(III), while the obtained pFe values are significantly lower (pFe: 14.95, 15.06; pH 7.4, c M = 1 µM, c L = 10 µM) compared to those of typical iron binders such as deferiprone or transferrin. The moderate gallium(III) and iron(III) binding ability of the compounds stands for lower solution complex stability compared to that of analogous bidentate non-substituted 3-hydroxy-2-pyridinone or 3-hydroxy-4-pyridinone (O,O) donor ligands. Tris-ligand complexes of the general formula [ML 3 ] (M = Ga, Fe) predominate at physiological pH for both ligands. No interaction with cell culture medium components was observed in the millimolar concentration range of gallium(III) complexes, however they can suffer significant decomposition at biologically relevant low concentrations leading to negligible cytotoxic activity. The redox potential of the studied iron–3-hydroxy-2-pyridinone complex (E 1/2 = −597 mV at pH 7.4) falls into the range that is typical of iron(III) complexes with conventional bidentate (O,O) donor-containing chelators. [ABSTRACT FROM AUTHOR]

The present work focused on the development of bioactive glass coatings employing Solution Precursor Plasma Spraying. Precursors of SiO 2 , CaO, Na 2 O and P 2 O 5 were mixed in distilled water to prepare concentrated solutions with a composition close to the 45S5 bioactive glass. Solutions were rheologically characterized to assess their stability with time and deposited onto AISI type 304 stainless steel to develop coatings under different parameters related to the thermal spraying technique. The effect of these parameters on coatings microstructure was studied by scanning electron microscopy. Coatings were also analysed by X–ray diffraction and scratch test to complete the microstructural characterization. Moreover, coatings bioactivity was evaluated by immersing them in Simulated Body Fluid. The study showed that using short spraying distances and low argon flow rates, gave rise to the typical microstructure derived from liquid feedstocks whereas some crystallization associated to the long spray distance used occurred. Scratch test revealed that the resulting coating possessed good mechanical properties when compared with similar coatings obtained by other plasma spraying techniques. Moreover, the obtained coating could develop an hydroxycarbonate apatite layer when in contact with Simulated Body Fluid as demonstrated by scanning electron microscopy, X–ray diffraction and Fourier transform infrared spectroscopy. • A 45S5 bioactive glass solution feedstock was synthesized stable for nine days. • Best conditions for feedstock deposition by SPPS were short spraying distance and low argon flow rate. • A well adhered and cohesive bioactive glass coating was developed. • Hydroxycarbonate apatite was nucleated on the coating surface after one day. • The microstructure revealed zones with different bioreaction rate. [ABSTRACT FROM AUTHOR]

Half-sandwich organometallic complexes of curcumin are extensively investigated as anticancer compounds. Speciation studies were performed to explore the solution stability of curcumin complexes formed with [Rh(η5-C 5 Me 5)(H 2 O) 3 ]2+. Acetylacetone (Hacac), as the simplest β-diketone ligand bearing (O,O) donor set, was involved for comparison and its Ru(η6‑ p ‑cymene), Ru(η6‑toluene) complexes were also studied. 1H NMR, UV–visible and pH-potentiometric titrations revealed a clear trend of stability constants of the acac complexes: Ru(η6‑ p ‑cymene) > Ru(η6‑toluene) > Rh(η5-C 5 Me 5). Despite this order, the highest extent of complex formation is seen for the Rh(η5-C 5 Me 5) complexes at pH 7.4. Formation constant of [Rh(η5-C 5 Me 5)(H 2 curcumin)(H 2 O)]+ reveals similar solution stability to that of the acac complex. Additionally, structures of two complexes were determined by X-ray crystallography. The in vitro cytotoxicity of curcumin was not improved by the complexation with these organometallic cations. Solution stability of Ru(II)(η6‑toluene), Ru(II)(η6‑ p ‑cymene) and Rh(III)(η5-C 5 Me 5) complexes of acetylacetone was determined in aqueous solution and compared with that of other (O,O) donor ligands. The structures of [Rh(III)(η5-C 5 Me 5)(H 2 curcumin)]+ and [Ru(II)(η5-toluene)(acetylacetonato)]+ were resolved by single crystal X-ray diffraction. Their cytotoxicity was evaluated in multidrug resistant human cancer cell lines. Unlabelled Image • Solution stability of Ru(arene) and Rh(C 5 Me 5) complexes of acac and curcumin • Acac is used as curcumin binding model. • X-ray crystal structures of two complexes and comparison with analogous structures • Antiproliferative activity against multidrug resistant human cancer cell lines • Human serum albumin binding and interaction with cell culture medium components [ABSTRACT FROM AUTHOR]

Abstract Cocrystal formation is a novel method to enhance physicochemical properties of pharmaceuticals. However, instability in solution is one of the challenging issues of cocrystals and surfactants/polymers could have a positive effect on cocrystal solubility and stability. In this study, tadalafil cocrystal was prepared via the solvent drop grinding method with methylparaben as a cocrystal former. The thermodynamic solubility of cocrystal was determined in phosphate buffer solution (pH = 6.8) and in the presence of different concentrations of sodium lauryl sulfate (SLS) and polyvinylpyrrolidone (PVP), followed by investigating their effects on solution stability of cocrystal. The prepared cocrystal showed enhancement in solubility compared with tadalafil, but the solution stability analysis indicated it is an incongruently saturating cocrystal that could transform to a less soluble solid form during slurring and dissolution. Moreover, PVP and SLS improved the cocrystal solution stability, however, the solubility advantage for the prepared cocrystal is not obtained because of preferential solubilization for tadalafil that is less soluble than methylparaben. Overall, the results showed that cocrystal formation of tadalafil with methylparaben has the ability to change its physicochemical properties. In addition, polymer and surfactant could have a significant effect on the solubility and the stability of the cocrystal. Graphical abstract Unlabelled Image Highlights • Cocrystal formation is a novel method to enhance physicochemical properties of pharmaceuticals. • Surfactants and polymers could have a positive effect on cocrystal solubility and stability. • The thermodynamic solubility of tadalafil-methyl paraben cocrystal was determined. • The applied polymer and surfactant could have a significant effect on the solubility and stability. [ABSTRACT FROM AUTHOR]

Solution stability attributes are one of the key parameters within the production and launching phase of new biopharmaceuticals. Instabilities of active biological compounds can reduce the yield of biopharmaceutical productions, and may induce undesired reactions in patients, such as immunogenic rejections. Protein solution stability thus needs to be engineered and monitored throughout production and storage. In contrast to the gold standard of long-term storage experiments applied in industry, novel experimental and in silico molecular dynamics tools for predicting protein solution stability can be applied within several minutes or hours. Here, a rheological approach in combination with molecular dynamics simulations are presented, for determining and predicting long-term phase behavior of highly concentrated protein solutions. A diversity of liquid phase conditions, including salt type, ionic strength, pH and protein concentration are tested in a Glutathione-S-Transferase (GST) case study, in combination with the enzyme with and without solubility-enhancing Cherry-Tag™. The rheological characterization of GST and Cherry-GST solutions enabled a fast and efficient prediction of protein instabilities without the need of long-term protein phase diagrams. Finally, the strong solubility enhancing properties of the Cherry-Tag™ were revealed by investigating protein surface properties in MD simulations. The tag highly altered the overall surface charge and hydrophobicity of GST, making it less accessible to alteration by the chemical surrounding. [ABSTRACT FROM AUTHOR]

Widespread applications of membrane technology call for the development of antifouling membranes, and preparation of mixed matrix membranes (MMMs) by mixing nanoparticles (NPs) into polymeric membrane matrix has attracted much attention. In this work, polyvinylidene fluoride (PVDF) MMMs were prepared by two TiO 2 sols with different NPs size (one from hydrolysis and condensation with an average size of 5 nm, and the other from dispersion of TiO 2 nanoparticles with a particle size of 21 nm), and comparison of their antifouling behaviours was conducted. Compared to the pristine PVDF membrane (N0) and membrane (N1) modified by TiO 2 sol from dispersion of TiO 2 NPs, the surface pore size, porosity and permeability of modified membrane (N2) by TiO 2 sol from hydrolysis and condensation were slightly decreased, while the hydrophilicity and the absolute value of Zeta potential were obviously improved. Moreover, the N2 membrane showed a higher surface energy barrier, smaller frequency shift in quartz crystal microbalance with dissipation monitoring, and higher relative flux than N1, indicating a better antifouling performance. The abundant hydroxyl groups and the increased Ti and O elements on the membrane surface accounted for the enhanced hydrophilicity and antifouling ability. Scanning electron microscope (SEM) images clearly show that TiO 2 particles were uniformly distributed for N2; however, the severe agglomeration and sedimentation were observed for N1. Multiple light scattering spectroscopy (MLiSSP) analysis showed that N2 casting solution had a higher stability as revealed by the negligible backscattering change, decreased demixing thickness and low turbiscan stability index (TSI) value. The different stability of casting solutions might result in the different NPs’ behaviours during membrane formation process, accounting for the discrepancy in the physicochemical properties and antifouling ability between N1 and N2 membranes. [ABSTRACT FROM AUTHOR]

The oxidized amyloses with high oxidation level and carboxyl content were successfully prepared through a two-step oxidation method using hydrogen peroxide as the oxidant and copper sulfate as the catalyst. The results showed that oxidation would prevent the oxidized product to crystallize and induce depolymerization of amylose molecules. Accordingly, the helices and inclusion capacity of oxidized amylose molecules were reduced. However, the solubility of oxidized amyloses in water was highly improved due to the introduced carboxyl groups. The solution stability of oxidized amylose-guest inclusion complexes in aqueous solution was efficiently improved to a large extent. The result suggested that the two-step oxidation method was an efficient way to highly broaden the applications of amylose-guest inclusion complexes in water environment. [ABSTRACT FROM AUTHOR]

We report the synthesis and characterization of a family of benzohydrazones (Ln, n = 1–6) derived from 2-carbaldehyde-8-hydroxyquinoline and benzylhydrazides containing different substituents in the para position. Their oxidovanadium(IV) complexes were prepared and compounds with 1:1 and 1:2 metal-to-ligand stoichiometry were obtained. All compounds were characterized by elemental analyses and mass spectrometry as well as FTIR, UV–visible absorption, NMR (ligand precursors) and EPR (complexes) spectroscopies, and by DFT computational methods. Proton dissociation constants, lipophilicity and solubility in aqueous media were determined for all ligand precursors. Complex formation with V(IV)O was evaluated by spectrophotometry for L4 (Me-substituted) and L6 (OH-substituted) and formation constants for mono [VO(HL)]+, [VO(L)] and bis [VO(HL) 2 ], [VO(HL)(L)]−, [VO(L) 2 ]2− complexes were determined. EPR spectroscopy indicates the formation of [VO(HL)]+ and [VO(HL) 2 ], with this latter being the major species at the physiological pH. Noteworthy, the EPR data suggest a different behaviour for L4 and L6, which confirm the results obtained in the solid state. The antiproliferative activity of all compounds was evaluated in malignant melanoma (A-375) and lung (A-549) cancer cells. All complexes show much higher activity on A-375 (IC 50 < 6.3 μM) than in A-549 cells (IC 50 > 20 μM). Complex 3 (F-substituted) shows the lowest IC 50 on both cell lines and lower than cisplatin (in A-375). Studies identified this compound as the one showing the highest increase in Annexin-V staining, caspase activity and induction of double stranded breaks, corroborating the cytotoxicity results. The mechanism of action of the complexes involves reactive oxygen species (ROS) induced DNA damage, and cell death by apoptosis. Synthesis, solution behaviour, and cytotoxicity of oxidovanadium(IV) complexes bearing 8-hydroxyquinoline benzohydrazide hydrazones. The compounds revealed good cytotoxicity on melanoma (A-375) and lung adenocarcinoma (A-549) cancer cell lines. Production of reactive oxygen species (ROS) with concomitant DNA double stranded break (DSB), caused cell death by apoptosis. [Display omitted] • VIVO forms complexes with versatile 8-hydroxyquinoline-hydrazides. • Formation constants for mono and bis complexes are determined. • Cytotoxicity on melanoma cell line occurs at low micromolar values. • Increase in reactive oxygen species induces DNA damage. • Annexin V and Caspase 3/7 flow cytometry confirm cell death by apoptosis. [ABSTRACT FROM AUTHOR]

This paper delivers a study on the change of rank of input matrix in Extreme Learning Machine (ELM) and the relationship between the rank of input matrix and the residence error of training an ELM. From the viewpoint of data analysis, the study reveals why ELM has a decreasing residence error with the increase of number of nodes in hidden layer and what role the Sigmoid function plays in increasing the rank of input matrix. Furthermore the relationship between the stability of solutions and the rank of output matrix is also discussed. An application of residence error to genetic algorithms of minimizing L 1 -norm ELM is given. [ABSTRACT FROM AUTHOR]

Thiosemicarbazones are promising candidates for anticancer therapy and their mechanism of action is often linked to their metal chelating ability. In this study, five (thio)semicarbazones with different donor sets (NNS, NNO, ONS, ONO) were selected and their behaviour in aqueous solution, the stability of their copper(II) complexes in addition to their cytotoxicity, DNA-binding, DNA cleavage ability and inhibition of topoisomerase IIα were investigated and compared. We aimed to reveal relationships between the structural variations, the significantly different physico-chemical properties, solution speciation and biological activity. The cytotoxicity of the ligands did not show correlation with the solubility, lipophilicity and permeability; and the decreased activity of the oxygen donor containing compounds was explained by their stronger preference towards chelation of iron(III) over iron(II). Meanwhile, among the copper complexes the most lipophilic species with the highest stability and membrane permeability exhibited the highest cytotoxicity. The studied copper(II) complexes interact with DNA, and reaction with glutathione led to heavy DNA cleavage in the case of the highly stable complexes which could be reduced in a reversible reaction with moderate rate. All the tested copper complexes inhibited topoisomerase IIα, however, this property of the complexes with low stability is most probably linked to the liberated free copper(II). Synopsis: Variation of the coordination modes in (thio)semicarbazone copper(II) complexes has a significant effect on the stability in solution, redox properties, cytotoxicity, DNA-binding, DNA cleavage ability and inhibition of topoisomerase IIα. [Display omitted] • Solution properties of five (thio)semicarbazone and their copper(II) complexes. • Semicarbazones are much weaker copper(II)-binders than the thiosemicarbazones. • Highly cytotoxic and stable copper thiosemicarbazone complexes. • All the studied copper(II) complexes are able to interact with DNA. • Copper(II)-thiosemicarbazonates induced the inhibition of TopoIIα. [ABSTRACT FROM AUTHOR]

Highlights: [•] New UPLC method for the determination of phenol impurities in ritonavir. [•] The predicted LOD and LOQ concentrations are very low for all three impurities. [•] The method was successfully applied for formulation batches of ritonavir. [•] Best suitable for monitoring of phenol impurities in ritonavir during its synthesis. [Copyright &y& Elsevier]

Highlights: [•] First report on simultaneous determination of four PGIs in zolmitriptan. [•] The developed UPLC–MS/MS method is highly sensitive and fully validated. [•] The detection levels of all four impurities are found to be very low. [•] The method is successfully applied for formulation batches of zolmitriptan. [Copyright &y& Elsevier]

Abstract: A successful parenteral formulation can be developed by studying stability and compatibility of biopharmaceuticals as a function of solution composition. Here, we evaluate the influence of pH, buffers, ionic strength, protein concentration and presence of excipients on recombinant human epidermal growth factor (rhEGF) stability. The stability was accessed by reversed-phase high performance liquid chromatography (RP-HPLC), size exclusion chromatography (SEC-HPLC), enzyme-linked immunosorbent assay (ELISA), Far-UV circular dichroism (CD) and light scattering. The overall maximal stability was obtained in pH near to 7.0 in phosphate, Tris and histidine buffers as the results of the different methods revealed. The CD results revealed that this protein is stable in an extensive pH range. Aggregation of rhEGF was minimized at pH values ranged from 6.0 to 8.0 as indicated the SEC-HPLC and light scattering results. Nor the ionic strength neither the rhEGF concentration had significant effect on the reaction rate constants. Most rhEGF–excipient instability occurs among this protein and reducing sugars. Polymers like poly(ethylene glycol) (PEG) and polysorbates increased methionine oxidation. The rhEGF oxidation and deamidation were the most common degradation pathways. This research identified critical solution factors to be considered for the development of a successful rhEGF parenteral formulation. [Copyright &y& Elsevier]

Abstract: Bioactive lipids derived from polyunsaturated fatty acids constitute an important set of lipid mediators with diverse homeostatic and pathophysiological activities. The role of bioactive lipids in inflammation, active resolution of inflammation, reproduction, cardiovascular biology, chronic diseases such as cancer and metabolic disorders is an active area of research. Other than the few clinically used eicosanoids such as prostaglandin F2α, prostacyclin, and prostaglandin E2, little is known about the stability of a majority of the bioactive lipids in aqueous solutions despite their extensive use under in vitro experimental conditions. The present study evaluated the stability of eicosanoids and docosanoids as well as their parent polyunsaturated fatty acids in tissue culture media with respect to incubation time, temperature, and composition of the media using multiple reaction monitoring (MRM) LC–MS. The results provide a comprehensive and valuable data set on the stability of these bioactive lipid mediators to guide in vitro experimentation. [Copyright &y& Elsevier]

Abstract: Strontium titanate SrTiO3 thin films have attracted interest as a possible gate dielectric material. Preparation of its high quality coatings is hindered by difference in volatility of the homometallic precursors – strontium beta-diketonates and titanium alkoxides. The only earlier known single-source precursor, a sec-alkoxide derivative Sr2Ti2(thd)4(OiPr)8, has limited volatility. Bimetallic primary alkyl chain complexes, Sr4Ti2O(thd)4(OR)10(ROH)2, R=Et, nPr, are stable and volatile, but possess a wrong composition. Highly volatile precursor Sr2Ti2(thd)4(OiBu)8 has been prepared using an iso-alkoxide, combining proper ligand size with the sterical requirements, and characterized by multivariate evaporation analysis. Its evaporation is associated with complete decomposition into homometallic species, which, however, are evaporated in a single step. This permits to successfully use this novel precursor for SrTiO3 thin film deposition by DLI-MOCVD technique in a sufficiently broad established temperature range. Using optimized experimental conditions, 100nm thick strontium titanate films with high permittivity have been successfully obtained on (100) Si. [Copyright &y& Elsevier]

Abstract: The solution stability of hydrophilic Keplerate polyoxometalate {Mo72Fe30} macroions was investigated at various ionic strengths. The solution stability varies with the type of monovalent cations with the lowest stability with large, weakly hydrated monovalent cations. Even lower stability was observed when the counter-cations were multivalent cations. Interestingly, the stability of {Mo72Fe30} solutions was found to increase with increasing POM concentration. The close association of monovalent counter-ions around macroions exists in aqueous solution and is likely enhanced at higher macroion concentrations. This behavior can further decrease the net charge on the macroions leading to a decreased electrostatic repulsion, which decreases the screening length of the macroions and causes them to irreversibly precipitate. [ABSTRACT FROM AUTHOR]

Abstract: A simple, precise and stability-indicating HPLC method was developed and validated for the simultaneous determination of bisoprolol fumarate and hydrochlorothiazide in pharmaceutical dosage form. The method involves the use of easily available inexpensive laboratory reagents. The separation was achieved on an Inertsil ODS 3V (25cm×4.6mm) 5μm column with isocratic flow. The mobile phase at a flow rate of 1.0mLmin−1, consisted of 0.1M potassium dihydrogen phosphate buffer and acetonitrile (70:30, v/v). The UV detection was carried out at 228nm. A linear response was observed over the concentration range 2.5–50μgmL−1 of bisoprolol fumarate and the concentration range 6.25–125μgmL−1 of hydrochlorothiazide. Limit of detection and limit of quantitation for bisoprolol fumarate were 0.01 and 0.03μgmL−1, respectively and for hydrochlorothiazide were 0.01 and 0.05μgmL−1, respectively. The method was successfully validated in accordance to ICH guidelines acceptance criteria for specificity, linearity, accuracy, precision, robustness, ruggedness and system suitability. Individual drugs (bisoprolol fumarate and hydrochlorothiazide), their combinations and the tablets were exposed to thermal, photolytic, hydrolytic and oxidative stress conditions. The resultant stressed samples were analyzed by the proposed method. The method gave high resolution among the degradation products and the analytes. The peak purity of analyte peaks in the stressed samples was confirmed by photodiode array detector. The method was used for accelerated stability study on marketed and in-house formulations. The analysis concluded that the method was selective for simultaneous estimation of bisoprolol fumarate and hydrochlorothiazide and was stability-indicating. [Copyright &y& Elsevier]

Abstract: The applicability of micellar electrokinetic capillary chromatography (MEKC) for the analysis of temozolomide (TMZ) and its degradants, 3-methyl-(triazen-1-yl)imidazole-4-carboxamide (MTIC) and 5-amino-imidazole-4-carboxamide (AIC) has been studied. Using short-end injection, the analysis of TMZ and its degradants could be performed within 1.2min. The obtained precision of migration times was better than 1.6RSD%, and the limit of quantitation (LOQ) was 0.31–0.93μg/mL. The therapeutic concentration of TMZ in blood samples can be determined after direct sample injection and conventional on-capillary UV detection. The proposed MEKC method was applied to study the stability of TMZ in water and serum at different pH values. It was established that the half-life of the TMZ in vitro serum at room temperature was 33min, close to the half-life (28min) obtained in water at pH 7.9. [Copyright &y& Elsevier]

Abstract: Trace analysis of unstable and reactive pharmaceutical genotoxic impurities (GTIs) is a challenging task in pharmaceutical analysis. Many method issues such as insufficient sensitivity, poor precision, and unusual (too high/low) spiking recovery are often directly related to analytes’ instability. We report herein a matrix deactivation approach that chemically stabilizes these analytes for analytical method development. In contrast to the conventional chemical derivatization approach where the analytes are transformed into stable detectable species, the matrix deactivation approach chemically deactivates the hypothetical reactive species in the sample matrix. The matrix deactivation approach was developed on the premise that the instability of certain analytes at trace level is caused by reactions between the analytes and low level reactive species in the sample matrix. Thus, quenching the reactivity of the reactive species would be a key to stabilizing the unstable and reactive analytes. For example, electrophilic alkylators could be destabilized by nucleophiles or bases through either nucleophilic substitution or elimination reactions. One way to mask those reactive species is via protonation by adding acids to the diluent. Alternatively, one can use nucleophile scavengers to deplete reactive unknown species in the sample matrix completely, in analogy to the use of antioxidants and metal chelators to prevent oxidation in the analysis of compounds liable to oxidation. This paper reports the application of the matrix deactivation to the analyses of unstable and reactive pharmaceutical genotoxic impurities. Some of the methods have been used to support development of manufacturing processes for drug substances and a recent regulatory filing. [Copyright &y& Elsevier]

Tests for chemical stability were carried out on carrier-added 68 Ge solutions prepared and calibrated in 2007 and 2011 to evaluate the suitability of the specific composition as a potential Standard Reference Material. Massic count rates of the stored solutions were measured using a NaI(Tl) well counter before and after gravimetric transfers. The present activity concentration of the 2007 solution was also measured using live-timed anticoincidence counting (LTAC) and compared to the 2007 calibrated value. The well counter data indicated no change in massic count rate to within uncertainties for either solution. The LTAC measurements gave a difference of −0.49% in the activity concentration 2007 solution over 7 years. However, the uncertainty in the decay correction over that time, due to the uncertainty in the 68 Ge half-life, accounted for the majority (0.67% out of 0.83%) of the standard uncertainty on the activity concentration. The results indicate that these carrier-added solutions are stable with regard to potential activity losses over several half-lives of 68 Ge. [ABSTRACT FROM AUTHOR]

Abstract: The calcitonin gene-related peptide (CGRP) receptor has been implicated in the pathogenesis of migraine. A class of urethanamide derivatives has been identified as potent inhibitors of the CGRP receptor. Compound 20 was found to be among the most potent (IC50 =17pM). It was shown to retain excellent aqueous solubility (>50mg/mL, pH 7) while dramatically improving solution stability as compared to our previously disclosed development candidate, BMS-694153 (1). [Copyright &y& Elsevier]

Abstract: Angiotensin-converting enzyme (ACE) inhibitors are a group of active substances binding to an active site of ACE. Many authors who studied the structure activity relationship suggested the structural elements needed for a potent ACE inhibitor. While many authors studied the activity of ACE inhibitor substances only a few structure stability studies have been presented. In this paper the stability properties of molecule xPRIL were studied by determination of degradation path and rate of degradation in aqueous solutions with different pH (2.0, 6.8 and 12.0) and temperatures (40, 60 and 80°C). The degradation of molecule through two main degradation paths was identified and confirmed by liquid chromatography and mass spectroscopy (LC–MS). Stability properties of xPRIL were determined in a stability study evaluated by high-performance liquid chromatography (HPLC). The first order kinetics of degradation reaction of xPRIL and Arrhenius equations for each pH were determined at observed conditions. xPRIL showed the highest stability at pH 2 solution. The degradation kinetics of xPRIL was compared to the degradation kinetics of enalapril maleate (EM) and perindopril (PER) in bio relevant solutions with pH 2.0 and 6.8. In addition to the stability study of xPRIL the forced degradation study of all three molecules at rigorous conditions was conducted. From the obtained results the structural element having the highest influence on stability properties of the studied molecules was identified. The fragmentation paths of xPRIL, its cyclization degradation product and its hydrolysis degradation product were identified and confirmed by MS/MS method. [Copyright &y& Elsevier]

Abstract: Bilevel optimization models, and more generally MPEC (mathematical program with equilibrium constraints) models, constitute important modelling tools in transportation science and network games, as they place the classic “what-if” analysis in a proper mathematical framework. The MPEC model is also becoming a standard for the computation of optimal design solutions, where “design” may include either or both of network infrastructure investments and various types of tolls. At the same time, it does normally not sufficiently well take into account possible uncertainties and/or perturbations in problem data (travel costs and demands), and thus may not a priori guarantee robust designs under varying conditions. We consider natural stochastic extensions to a class of MPEC traffic models which explicitly incorporate data uncertainty. In stochastic programming terminology, we consider “here-and-now” models where decisions on the design must be made before observing the uncertain parameter values and the responses of the network users, and the design is chosen to minimize the expectation of the upper-level objective function. Such a model could, for example, be used to derive a fixed link pricing scheme that provides the best revenue for a given network over a given time period, where the varying traffic conditions are described by distributions of parameters in the link travel time and OD demand functions. For a general such SMPEC network model we establish not only the existence of optimal solutions, but in particular their stability to perturbations in the probability distribution. We also provide convergence results for general algorithmic schemes based on the penalization of the equilibrium conditions or possible joint upper-level constraints, as well as for algorithms based on the discretization of the probability distribution, the latter enabling the utilization of standard MPEC algorithms. Especially the latter part utilizes relations between the traffic application of SMPEC and stochastic structural topology optimization problems. [Copyright &y& Elsevier]

Abstract: In this paper, a new method for solving the perspective-n-point (PnP) problem is developed. With an auxiliary point, the linear method for the special case of four coplanar points is extended to find the coarse solutions for the general P3P problem. A recursive least square algorithm with a forgetting factor is introduced to find all the accurate solutions for the P3P problem. Then the algorithm is extended to the general PnP problem. The solution stability issues are investigated for the P3P, P4P and P5P problem, respectively. Furthermore, a pattern is designed to ensure unique solution for the PnP problem. Experiments are performed to verify the effectiveness of the proposed method. [Copyright &y& Elsevier]

Abstract: Perindopril Erbumine (PER) is one of the newly used angiotensin-converting enzyme inhibitors (ACE inhibitors) and is used for the treatment of patients with hypertension and symptomatic heart failure. It has two main degradation pathways, i.e. the degradation by hydrolysis and the degradation by cyclization. An isothermal heat conduction microcalorimetry (MC) and high pressure liquid chromatography (HPLC) were used for the characterization of aqueous solutions of PER and its stability properties. The rates of heat evolved during degradation of perindopril were measured by MC as a function of temperature and pH and from these data rate constant and change in enthalpy of the reactions were determined. With the HPLC method the concentration of perindopril and its degradation products were measured as a function of time in aqueous solutions of different pH that were stored at different temperatures. We demonstrated that reactions of degradation of perindopril at observed conditions follow the first order kinetics. The Arrhenius equation for each pH was determined. At pH 6.8 only one degradation pathway is present, i.e. the degradation by hydrolysis. Degradation constants for this pathway calculated from MC data are in good agreement with those obtained from HPLC. MC as a non-specific technique was shown to be useful in studies of PER when one reaction was present in the sample and also when more chemical and physical processes were simultaneously running. [Copyright &y& Elsevier]

Abstract: Structural characteristics of keratin regenerated from water (KW) and from formic (KF) acid solutions were compared. Amino acid composition and molecular weight distribution of KW and KF samples were studied by high performance liquid chromatography (HPLC) and SDS-PAGE electrophoresis. Turbidity measurement showed that keratin dissolved in formic acid forms transparent and stable solutions and no flocculation occurs. In addition, because of its good solvation properties, studied by viscosity measurements, formic acid can be used as a co-solvent to prepare keratin-based blend solutions. Structural studies carried out by X-ray diffraction (XRD), Fourier transform infrared (FT-IR) and near infrared (NIR) suggest that formic acid stabilizes the β-sheet structure. Thermogravimetric analysis (TGA) reveals a higher thermal stability of keratin regenerated from formic acid with respect to keratin regenerated from water. [Copyright &y& Elsevier]

Abstract: The modification of zirconium or hafnium alkoxides with diethanolamine, H2dea, leads to the formation of unique nona-coordinated M{μ-η3-NH(C2H4O)2}3 cores. The mechanism is used to develop a self-assembly approach to the first thermodynamically stable zirconium–titanium and hafnium–titanium precursors, Zr{μ-η3-NH(C2H4O)2}3[Ti(O i Pr)3]2 (1) and Hf{μ-η3-NH(C2H4O)2}3[Ti(O i Pr)3]2 (2). Mass spectrometric characterization of these compounds demonstrates their volatility. In addition to the solution stability of these compounds the volatility makes them attractive single source precursors for MOCVD and ALD applications. These precursors are also interesting candidates for application in sol–gel synthesis of microporous materials as the stability of the core prevents self-assembly of ligands on the outer surface of the primary particles formed during the hydrolysis. A n-propoxide analog of 1 can be prepared from zirconium n-propoxide but does not yield any crystalline material. It is demonstrated that 1 can be prepared from [Zr(O n Pr)(O i Pr)3( i PrOH)]2, however, with a lower yield compared to the use of zirconium isopropoxide. The single crystals obtained from systems containing zirconium isopropoxide, titanium isopropoxide and triethanolamine H3tea turned out to be Ti2(O i Pr)2({μ-η4-NH(C2H4O)3}2)2 (4). Theoretical calculations indicate that the octacoordinate M{μ-η4-N(C2H4O)3}2 core, anticipated in reaction with H3tea, will have metal–nitrogen bonds that are too long for its stabilization. This explains why the formation of 4 is thermodynamically favored over the formation of heterometallic species. [Copyright &y& Elsevier]

Abstract: A novel stability-indicating high-performance liquid chromatographic assay method was developed and validated for docetaxel in the presence of degradation products generated from forced decomposition studies. A gradient HPLC method was developed to separate the drug from the degradation products, using a Hichrom RPB HPLC column. Mixture of water and acetonitrile was used as mobile phase. The flow rate was 1.0ml/min and the detection was done at 230nm. Using the above method one can carry out the quantitative estimation of impurity namely DCT-1 and docetaxel. The developed gradient LC method was subsequently validated. [Copyright &y& Elsevier]

In this paper, the regenerated silk fibroin (SF) solution dissolved in formic acid was used as a model protein to understand the role of formic acid in solution stability and crystallization of protein-based materials. The molecular decomposition of SF did not occur for the dissolution process in formic acid within 1–2 days of storage times. The β-sheet crystallization of SF molecules was occurred by the elimination of formic acid upon drying. The SF molecules in formic acid solution are stable and have low hydrodynamic radius values. This may be closely related to the fact that formic acid has two opposite functions of dissolution and crystallization simultaneously. The turbidity, dynamic light scattering and FTIR measurements elucidate that the solution stability and crystallization of SF are attributed to compact molecular shape of SF in formic acid, resulted from the molecular interactions between formic acid and polar groups in SF molecules. [Copyright &y& Elsevier]

The solution chemical properties such as proton dissociation, complex formation with copper(II) and gallium(III) ions in addition to antibacterial and antitumor activity of a novel tridentate salicyaldehyde semicarbazone-estrone hybrid (estrone-SC) and a related bicyclic compound (thn-SC) were investigated. The crystal structure of complex [Cu(thn-SC H −1)Cl] was studied by single crystal X-ray diffraction method. Estrone-SC and thn-SC form mono-ligand complexes with Cu(II) characterized by relatively high stability, however, they are much less stable than their thiosemicarbazone analogues. The neutral Cu(II) complexes with (O−,N,O−)(H 2 O) coordination mode predominate at physiological pH. Estrone-SC and thn-SC are more efficient Ga(III) binders in comparison with thiosemicarbazones, although the complexes also suffer dissociation at pH 7.4. The Cu(II) complex of estrone-SC displayed significant cytotoxicity in A549, SW480 and CH1/PA cancer cells, and moderate apoptosis induction and ROS formation. The semicarbazone compounds did not exhibit antibacterial effect; unlike the related Cu(II)-thiosemicarbazone complexes represented by the fairly low MIC values (3–50 μM) obtained on the Gram-positive Staphylococcus aureus and Enterococcus faecalis bacteria. A salicylaldehyde semicarbazone-estrone hybrid and its complexation with Cu(II) and Ga(III) was studied. The exchange of S to O in the thiocarbamoyl moiety results in significant effect on p K a , complex stability, antitumor and antibacterial activity. [Display omitted] • A novel tridentate salicyaldehyde semicarbazone-estrone hybrid. • Significantly higher stability complexes formed with Cu(II) than with Ga(III). • Estrone hybridization results in the higher solution stability of the complexes. • Cytotoxicity of the semicarbazone-estrone hybrid is enhanced upon Cu(II) complexation. • Exchange of S to O in the thiocarbamoyl moiety strongly influences the bioactivities. [ABSTRACT FROM AUTHOR]

Abstract: Single crystals of pure and potassium halides additive mixed l-arginine phosphate monohydrate have been grown with good optical quality by slow temperature reduction method. Microbial growth aspects and coloration have been studied on the growth solutions. In addition to that the structural properties have been studied by powder X-ray diffraction method and Fourier transform infrared spectral analyses for the grown crystals. Thermal stability of the grown crystals were studied by thermo gravimetric (TG) and differential thermal analyses (DTA) and found that the grown crystals are suitable for device fabrication for frequency conversion applications. [Copyright &y& Elsevier]

The metastable zone width and induction period of ZTS solution have been measured to investigate the influence of H 3 PO 4 on solution stability, and it could be improved by adding phosphoric acid. Pure and H 3 PO 4 doped ZTS crystals have been successfully grown using the slow-cooling method in aqueous solution. Several crystal samples were characterized by XRD, FTIR, TG, DTA, DTG, UV-VIS and SHG. The results show that some changes have taken place on external morphology and internal structure after H 3 PO 4 -doping. Thermostability, light transmittance and SHG efficiency of ZTS crystals are also affected by H 3 PO 4 , and all of them become better than undoped crystal, which are meaningful for practical applications of crystals. • ZTS solution stability was investigated by measuring metastable zone width and induction period. • ZTS crystals were grown using slow-cooling method in aqueous solution. • Impacts of H 3 PO 4 on ZTS solution stability, crystal growth and crystal property. [ABSTRACT FROM AUTHOR]

Abstract: Stability of raw TATP (3,3,6,6,9,9-hexamethyl-1,2,4,5,7,8-hexoxonane) samples in solutions of common solvents was studied to highlight problems faced by forensic labs in identification and analysis of organic peroxide samples. The TATP samples were prepared by reaction of acetone and hydrogen peroxide (30%) with the aid of following catalysts: hydrochloric, sulfuric, nitric, perchloric and methanesulfonic acid. Acetone, acetonitrile, methanol and acetonitrile/water solutions of TATP samples were prepared and stored at 50°C. Various degrees of stability were observed for particular combination of catalyst and solvent ranging from totally unstable (catalyst–H2SO4/any solvent) to very stable (catalyst-HCl/solvent acetonitrile). Purification of crude TATP by re-crystallization results in product stable in all investigated solvents. Stability of solution prepared from re-crystallized DADP (3,3,6,6-tetramethyl-1,2,4,5-tetroxane) was found to be on the same level as the stability of solution of re-crystallized TATP. [Copyright &y& Elsevier]

Half-sandwich organometallic complexes featuring Ru(II), Os(II) and Rh(III) metal centers and naturally occurring bidentate 2-hydroxy-[1,4]-naphthoquinone ligands (lawsone and phthiocol) have been synthesized and characterized in both solid state and solution phase by analytical, spectroscopic, electrochemical and single crystal X-ray diffraction techniques. Comparative studies revealed the influence of the respective metal center (Ru, Os, Rh), leaving group (Cl, Br, I) and arene (p -cymene, toluene, pentamethylcyclopentadienyl), as well as the naphthoquinone ligand on the structural properties and solution speciation. Additionally, cytotoxicity was tested in SW480, CH1/PA-1 and A549 human cancer cell lines showing a broad range of IC 50 values. Image 1 • Single crystal X-ray structure of five half-sandwich phthiocol complexes. • Anticancer activity in three human cancer cell lines. • Solution stability of Ru(II) and Rh(III) complexes of 2-hydroxy-[1,4]-naphthoquinones. • Comparison with other bidentate (O,O) ligands. [ABSTRACT FROM AUTHOR]

Solution chemical properties of two bidentate pyrazolyl thiosemicarbazones 2-((3-methyl-1-phenyl-1 H -pyrazol-4-yl)methylene)hydrazinecarbothioamide (Me-pyrTSC), 2-((1,3-diphenyl-1 H -pyrazol-4-yl)methylene)hydrazinecarbothioamide (Ph-pyrTSC), stability of their Cu(II) and Ru(η6- p -cymene) complexes were characterized in aqueous solution (with 30% DMSO) by the combined use of UV–visible spectrophotometry, 1H NMR spectroscopy and electrospray ionization mass spectrometry in addition to their solid phase isolation. The solid phase structures of Me-pyrTSC∙H 2 O, [Ru(η6- p -cymene)(Me-pyrTSC)Cl]Cl and [Cu(Ph-pyrTSCH −1) 2 were determined by single crystal X-ray diffraction. High stability mononuclear Ru(η6- p -cymene) complexes with (N,S) coordination mode are formed in the acidic pH range, and increasing the pH the predominating dinuclear [(Ru(η6- p -cymene)) 2 (L) 2 2+ complex with μ 2 -bridging sulphur donor atoms is formed (where L− is the deprotonated thiosemicarbazone). [CuL]+ and [CuL 2 complexes show much higher stability compared to that of complexes of the reference compound benzaldehyde thiosemicarbazone. [CuL 2 complexes predominate at neutral pH. Me-pyrTSC and Ph-pyrTSC exhibited moderate cytotoxicity against human colonic adenocarcinoma cell lines (IC 50 = 33–76 μM), while their complexation with Ru(η6- p -cymene) (IC 50 = 11–24 μM) and especially Cu(II) (IC 50 = 3–6 μM) resulted in higher cytotoxicity. Cu(II) complexes of the tested thiosemicarbazones were also cytotoxic in three breast cancer and in a hepatocellular carcinoma cell line. No reactive oxygen species production was detected and the relatively high catalase activity of SUM159 breast cancer cells was decreased upon addition of the ligands and the complexes. In the latter cell line the tested compounds interfered with the glutathione synthesis as they decreased the concentration of this cellular reductant. Solution stability of anticancer Ru(II)(η6- p -cymene) and Cu(II) complexes of two bidentate pyrazolyl thiosemicarbazones (TSC) was determined, and three structures were resolved by X-ray diffraction. [(Ru(η6- p -cymene)) 2 (TSC) 2 2+ and [Cu(TSC) 2 complexes are the dominant species at neutral pH. The metal complexes are more cytotoxic than the ligands. Unlabelled Image • Solution stability of Ru(cymene) and Cu(II) pyrazolyl thiosemicarbazone complexes • Dinuclear Ru(cymene) species with (N,S) donor and μ2-bridging S atoms at neutral pH • [CuL 2 with (N,S)(N,S) donor set predominates at neutral pH • Solid phase structures of two complexes and one ligand resolved by X-ray diffraction • More cytotoxic metal complexes than the ligands in various human cancer cell lines [ABSTRACT FROM AUTHOR]