Characterization of currently marketed heparin products: key tests for quality assurance

During the 2007–2008 heparin crisis, it was found that the United States Pharmacopeia (USP) testing monograph for unfractionated heparin sodium (UFH) did not detect the presence of the contaminant, oversulfated chondroitin sulfate (OSCS) in heparin. In response to this concern, new tests and specifications were developed by the Food and Drug Administration (FDA) and USP and put in place to not only detect the contaminant OSCS but also to improve assurance of quality and purity of the drug product. Additional tests were also developed to monitor the heparin supply chain for other possible economically motivated additives or impurities. In 2009, a new USP monograph was put in place that includes 500 MHz ¹H NMR, SAX-HPLC, %galactosamine in total hexosamine, and anticoagulation time assays with purified factor IIa or factor Xa. These tests represent orthogonal approaches for UFH identification, measurement of bioactivity, and for detection of process impurities or contaminants in UFH. The FDA has applied these analytical approaches to the study of UFH active pharmaceutical ingredients in the marketplace. Here, we describe results from a comprehensive survey of UFH collected from seven different sources after the 2009 monograph revision and compare these data with results obtained on other heparin samples collected during the 2007–2008 crisis.     

3D graphical representation of protein sequences and their statistical characterization

Based on three physicochemical properties of amino acid side chains, we proposed a novel unique 3D graphical representation of protein sequences. Then, we constructed two vectors of three components as mathematical objects to characterize protein sequences numerically. The similarity/dissimilarity analysis among nine ND5 protein sequences proved the utility of our approach. A correlation and significance analysis have been provided to compare our results and the sequence homology.     

High surface area nano-sized La0.6Ca0.4MnO3 perovskite powder prepared by low temperature pyrolysis of a modified citrate gel

Single phase nanocrystalline La_0.6Ca_0.4MnO₃ powder was synthesized by both the usual and a modified citrate gel precursor method, and the effects on the formation of homogeneous nano-sized powder with a perovskite structure were investigated. In the modified method, single phase La_0.6Ca_0.4MnO₃ powder with an average particle size of 17.2 nm was obtained when the powder was pyrolyzed at 520°C for 2 h. Its specific surface area was 40.7 m² g⁻¹, about 4-fold larger than that of powder made by the usual citrate gel method.      

Organic–inorganic hybrid of anchored dicationic ionic liquid on Al‐MCM‐41‐phosphovanadomolybdate toward selective oxidation of benzene to phenol

A phosphovanadomolybdate hybridized with an anchored dicationic ionic liquid on Al‐MCM‐41 was prepared through the anion exchange and characterized by ¹H and ¹³C NMR, FTIR, UV–Vis, XRD, XPS, TGA, TEM, FESEM, ICP‐OES and BET techniques. The obtained data demonstrated that the composite is a porous material with the high surface area and also having a large pore volume which are 405 m² g^?1 and 0.616 cm³ g^?1 respectively. The prepared composite has shown an acceptable catalytic activity for converting benzene selectively to phenol with hydrogen peroxide as eco‐friendly oxidant. Under the optimized reaction conditions, the hybrid catalyst resulted in phenol yield of 14.8% with 100% selectivity and a TOF value of 20.0 h^?1. The catalyst also revealed a desired recovery and reusability. The efficient performance of the composite is related to the textural and polyoxometalate properties.     

Zeros and poles of output voltage of 3-terminal potentiometer networks

Zusammenfassung Betrachtet wird eine 3-Pol-Schaltung, die feste Widerstände und endlich viele lineare Potentiometer auf einer gemeinsamen Achse enthält. Wenn diese Schaltung von einer konstanten SpannungE ₁ gespeist ist, dann ist die AusgangsspannungE ₂ an einem beliebigen Punkt der Schaltung eine rationale Funktion vonx, wobeix den Drehwinkel der Achse bedeutet (0x1).In dieser Arbeit wird folgender Satz bewiesen: «Die Nullstellen vonE ₂ sind entweder reell ausserhalb des Intervalls 0<x<1, oder konjugiert-komplex. Die Pole vonE ₂ sind einfach, reell, negativ oder >1.»     

Optimized hybrid dielectrophoretic microchip for separation of bioparticles

Point-of-care diagnostics requires a smart separation of particles and/or cells. In this work, the multiorifice fluid fractionation as a passive method and dielectrophoresis-based actuator as an active tool are combined to offer a new device for size-based particle separation. The main objective of the combination of these two well-established techniques is to improve the performance of the multiorifice fluid fractionation by taking advantage of dielectrophoresis-based actuator for separating particles. Initially, by using numerical simulations, the effect of using dielectrophoresis-based actuator in multiorifice fluid fractionation on the separation of particles was investigated, and the size of the device was optimized by 25% compared to a device without dielectrophoresis-based actuator. Also, adding dielectrophoresis-based actuator to multiorifice fluid fractionation can extend the range of flow rates needed for separation. In the absence of dielectrophoresis-based actuator, the separation took place only when the flow rate is 100 μL/min, in the presence of dielectrophoresis-based actuator (20 Vp-p), the separation happened in flow rates ranging from 70 to 120 μL/min.     

Characterization of currently marketed heparin products: analysis of molecular weight and heparinase-I digest patterns

We evaluated polyacrylamide gel electrophoresis (PAGE) and size exclusion chromatography coupled with multi-angle laser light scattering (SEC-MALLS) approaches to determine weight-average molecular weight (M _w) and polydispersity (PD) of heparins. A set of unfractionated heparin sodium (UFH) and low-molecular-weight heparin (LMWH) samples obtained from nine manufacturers which supply the US market were assessed. For SEC-MALLS, we measured values for water content, refractive index increment (dn/dc), and the second virial coefficient (A ₂) for each sample prior to molecular weight assessment. For UFH, a mean ± standard deviation value for M _w of 16,773 ± 797 was observed with a range of 15,620 to 18,363 (n = 20, run in triplicate). For LMWHs by SEC-MALLS, we measured mean M _w values for dalteparin, tinzaparin, and enoxaparin of 6,717 ± 71 (n = 4), 6,670 ± 417 (n = 3), and 3,959 ± 145 (n = 3), respectively. PAGE analysis of the same UFH, dalteparin, tinzaparin, and enoxaparin samples showed values of 16,135 ± 643 (n = 20), 5,845 ± 45 (n = 4), 6,049 ± 95 (n = 3), and 4,772 ± 69 (n = 3), respectively. These orthogonal measurements are the first M _w results obtained with a large heparin sample set on product being marketed after the heparin crisis of 2008 changed the level of scrutiny of this drug class. In this study, we compare our new data set to samples analyzed over 10 years earlier. In addition, we found that the PAGE analysis of heparinase digested UFH and neat LMWH samples yield characteristic patterns that provide a facile approach for identification and assessment of drug quality and uniformity.     

Investigation on rough rice drying kinetics at various thin layers of a deep bed

Moisture content gradients along the bed column are commonly neglected during simulation of deep-bed grain drying. In this study, rough rice drying kinetics at various thin layers of a deep bed was investigated. The experiments were conducted under different drying conditions and the data were compared with the values predicted by a previously developed non-equilibrium model for numerical simulation of grain drying. The moisture content gradients related to the rough rice column indicated that the higher the drying layer, the more was the moisture content at each drying time. The constant drying rate period was observed neither for any thin layers nor for the entire drying column. The drying rate of the lower layers continuously decreased with drying time, whereas that of the upper layers firstly increased and then decreased. The implemented model predicted drying process with a high accuracy at various layers. However, the values of maximum relative error (RE _max ) and mean relative error (MRE) increased as the air temperature increased, and reversely decreased with the air velocity. The higher values of MRE and RE _max were related to the layer 1 (0–5 cm bed height) at temperature of 60 °C and air velocity of 0.4 m s^?1, and the lower values belonged to the layer 4 (15–20 cm bed height) at temperature of 40 °C and air velocity of 0.9 m s^?1.     

Green phenol hydroxylation by ultrasonic-assisted synthesized Mg/Cu/Al-LDH catalyst with different molar ratios of Cu2+/Mg2+

Nitrate-intercalated Mg/Cu/Al-layered double hydroxides (LDHs) were successfully synthesized by the co-precipitation method under ultrasonic irradiation as a fast, simple, and low-cost technique. The LDHs were synthesized with six different molar ratios of Cu²⁺/Mg²⁺, and then they were characterized by FT-IR, XRD, TGA, ICP, BET, TEM, and FE-SEM analyses. The results showed that the nitrate ions were well intercalated between layers without any carbonate ions. According to the XRD and TGA results, increasing of Cu ions in the LDHs lowered the crystallization and improved the thermal stability of samples at the same time. The morphological studies carried out by FE-SEM and TEM analyses showed the morphological structure similar to the lamellar structure and plate-like shape particles. However, the surface property of binary LDHs, including Al and only one of Cu or Mg elements, was better than ternary ones. Furthermore, this catalyst was used for the phenol hydroxylation using H₂O₂ as oxidant and water as a solvent. The results exhibit that the CuMg₃₂Al-NO^3? catalyst had the best catalytic activity, as well as it was found that the catalyst is active under mild reaction conditions such as the temperature of 65 °C, phenol: oxidant ratio of 2:1, phenol/catalyst?=?100, and reaction time of 1 h. Thus, these conditions gave better activity with the conversion of 27%, the selectivity of 92.05% for catechol and hydroquinone, and CAT/HQ ratio of 1.5.

     

Reactions with Stilbenes and Related Derivatives. Part I. Reactions of 1, 2-Dihalogeno-1, 2-bis-(4-methoxyphenyl)ethanes with Alcohols

The reaction of 1, 2-dibromo-1, 2-bis(4-methoxyphenyl)ethane with alcohols was associated with rearrangement to give the corresponding bis(4-methoxyphenyl)acetals. In boiling ethylene glycol 4,4′-dimethoxy-deoxybenzoin was also obtained due to an aldehyde-ketone rearrangement. 4,4′-Dimethoxybenzophenone was also formed being apparently derived from the acetals. The mechanism of formation of the acetals has been discussed.