Highly sensitive and rapid determination of tacrolimus in peripheral blood mononuclear cells by liquid chromatography–tandem mass spectrometry

After solid organ transplantation, tacrolimus is given to prevent rejection. Therapeutic drug monitoring is used to reach target concentrations of tacrolimus in whole blood. Because the site of action of tacrolimus is the lymphocyte, and tacrolimus binds ~80% to erythrocytes, the intracellular tacrolimus concentration in lymphocytes is possibly more relevant. For this purpose, we aimed to develop, improve and validate a UPLC–MS/MS method to measure tacrolimus concentrations in isolated peripheral blood mononuclear cells (PBMCs). PBMCs were isolated using a Ficoll separation technique, followed by a washing step using red blood cell lysis. A cell suspension of 50 μL containing 1 million PBMCs was used in combination with MagSiMUS‐TDM^PREP. To each sample we added 30 μL lysis buffer, 20 μL reconstitution buffer containing ¹³C²H₄‐tacrolimus as internal standard, 40 μL MagSiMUS‐TDM^PREP Type I Particle Mix and 175 μL Organic Precipitation Reagent VI for methanol‐based protein precipitation. A 10 μL aliquot of the supernatant was injected into the UPLC–MS/MS system. The method was validated, resulting in high sensitivity and specificity. The method was linear (r² = 0.997) over the range 5.0–1250 pg/1 × 10⁶ PBMCs. The inaccuracy was <5% and the imprecision was <15%. The washing steps following Ficoll isolation could be performed at either room temperature or on ice, with no effect of the temperature on the results. A method for the analysis of tacrolimus concentrations in PBMCs was developed and successfully validated. Further research will be performed to investigate the correlation between concentrations in PBMCs and clinical outcome.     

Rapid and easy quantification of elemental sulphur in aqueous samples from biological reactors: the turbidimetric method revisited

Recent developments in wastewater treatment have led to a renewed interest to obtain elemental sulphur (S°) as a by-product from bioreactors. However, practical studies are limited by the gap of adequate analytical techniques for its determination. This paper provides a statistical study and matrix effect evaluation of an adapted spectrophotometric method for routine S° analyses in aqueous samples, based on a methodology previously described by Hart (1961). Four complex matrices were tested: domestic sewage and effluent samples from three different bioreactors. Tested performance criteria included linearity, matrix effect, limit of detection and quantification and S° recovery. Results were linear (R² = 0.99994) in the studied range (5 to 100 mg S° L^?1) and no matrix effect was observed. The accuracy was based on recovery values that varied from 100% to 106%. The colloidal S° separation and extraction protocol was also considered suitable for aqueous samples, reaching more than 99.0% of S° recovery.     

The h-SbxWO3+2x Oxygen Excess Antimony Tungsten Bronze

We describe the previously unreported oxygen excess hexagonal antimony tungsten bronze with composition Sb_0.5W₃O₁₀, in the following denoted as h-Sb_xWO_3+2x with x=0.167, to demonstrate its analogy to classical A_xWO₃ tungsten bronzes. This compound forms in a relatively narrow temperature range between 580 °C<T<620 °C. It was obtained as a dark-blue polycrystalline powder, and as thin, needle-shaped, blue single crystals. h-Sb_xWO_3+2x crystallizes in the hexagonal space group P6/mmm with the cell parameters a=7.4369(4) Å and c=3.7800(2) Å. The antimony and excess oxygen occupy the hexagonal channels within the network of corner-sharing WO₆ octahedra. h-Sb_xWO_3+2x has a resistivity of ρ_{300 K}≈1.28 mΩ cm at room temperature, with little if any temperature-dependence on cooling. DFT calculations on a simplified model for this compound find a metallic-like electronic structure with the Fermi level falling within rather flat bands, especially around the Γ point.     

Paramagnetic Lanthanide NMR Probes Signalling Changes in Zinc Concentration by Emission and Chemical Shift: A Proof of Concept Study

A zinc-selective probe based on a set of rare earth complexes of a modified DO3A macrocyclic ligand incorporating a tris-pyridylamine (TPA) moiety has been structurally characterised in solution and in the solid-state. One pyridine group possesses a tert-butyl substituent to serve as an NMR reporter group. The mono-capped square-antiprismatic Dy complex has a long bond (2.83 Å) to an apical N atom (pK_a 5.70 Eu) and binds to one water molecule on zinc binding. Zinc binding is reversible and involves all of the exocyclic ligand N donors; it is signalled by large (ratiometric) changes in Eu emission intensity, and by dramatic changes in the size (>50 ppm) and sign of the chemical shift of the paramagnetically shifted tBu resonances in Tb, Dy and Tm complexes. Slow trans-metallation was observed, leading to formation of an unusual di-zinc species in which one zinc ion is seven-coordinate and the other is six-coordinate.     

Single‐Walled Carbon Nanotubes in Highly Viscous Media: A Comparison between the Dispersive Agents [BMIM][BF4], L121, and Triton X‐100

Dispersions of single‐walled carbon nanotubes (SWNTs) have been prepared by using the room‐temperature ionic liquid [BMIM][BF₄] (1‐butyl‐3‐methylimidazolium tetrafluoroborate), the triblock copolymer Pluronic L121 [poly(ethylene oxide)₅‐poly(propylene oxide)₆₈‐poly(ethylene oxide)₅] and the non‐ionic surfactant Triton X‐100 (TX100) in the pure state. The size of the SWNTs aggregates and the dispersion degree in the three viscous systems depend on the sonication time, as highlighted by UV/Vis/NIR spectroscopy and optical microscopy analysis. A nonlinear increase in conductivity can be observed as a function of the SWNTs loading, as suggested by electrochemical impedance spectroscopy. The generation of a three‐dimensional network of SWNTs showing a viscoelastic gel‐like behavior above a critical percolation concentration has been found at 25 °C in all the investigated systems by oscillatory rheology measurements.     

Synthesis and characterization of double hydrophilic block copolymers containing semi-rigid and flexible segments

3-Methyl-(E)-stilbene (3MSti) and 4-(diethylamino)-(E)-stilbene (DEASti) monomers are synthesized and polymerized separately with maleic anhydride (MAn) in a strictly alternating fashion using reversible addition-fragmentation chain transfer (RAFT) polymerization techniques. The optimal RAFT chain transfer agents (CTAs) for each copolymerization affect the reaction kinetics and CTA compatibilities. Psuedo-first order polymerization kinetics are demonstrated for the synthesis of poly((3-methyl-(E)-stilbene)-alt-maleic anhydride) (3MSti-alt-MAn) with a thiocarbonylthio CTA (methyl 2-(dodecylthiocarbonothioylthio)−2-methylpropionate, TTCMe). In contrast, a dithioester CTA (cumyl dithiobenzoate, CDB) controls the synthesis of poly((4-(diethylamino)-(E)-stilbene)-alt-maleic anhydride) (DEASti-alt-MAn) with pseudo-first order polymerization kinetics. DEASti-alt-MAn is chain extended with 4-acryloylmorpholine (ACMO) to synthesize diblock copolymers and subsequently converted to a double hydrophilic polyampholyte block copolymers (poly((4-(diethylamino)-(E)-stilbene)-alt-maleic acid))-b-acryloylmorpholine) (DEASti-alt-MA)-b-ACMO) via acid hydrolysis. The isoelectric point and dissociation behavior of these maleic acid-containing copolymers are determined using ζ-potential and acid–base titrations, respectively. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 219–227     

Assessing the Importance of Cation Size in the Tetragonal-Cubic Phase Transition in Lithium-Garnet Electrolytes**

Lithium garnets are promising solid-state electrolytes for next-generation lithium-ion batteries. These materials have high ionic conductivity, a wide electrochemical window and stability with Li metal. However, lithium garnets have a maximum limit of seven lithium atoms per formula unit (e.g., La₃Zr₂Li₇O₁₂), before the system transitions from a cubic to a tetragonal phase with poor ionic mobility. This arises from full occupation of the Li sites. Hence, the most conductive lithium garnets have Li between 6–6.55 Li per formula unit, which maintains the cubic symmetry and the disordered Li sub-lattice. The tetragonal phase, however, forms the highly conducting cubic phase at higher temperatures, thought to arise from increased cell volume and entropic stabilisation permitting Li disorder. However, little work has been undertaken in understanding the controlling factors of this phase transition, which could enable enhanced dopant strategies to maintain room temperature cubic garnet at higher Li contents. Here, a series of nine tetragonal garnets were synthesised and analysed by variable temperature XRD to understand the dependence of site substitution on the phase transition temperature. Interestingly the octahedral site cation radius was identified as the key parameter for the transition temperature with larger or smaller dopants altering the transition temperature noticeably. A site substitution was, however, found to make little difference irrespective of significant changes to cell volume.     

Essential oil and fractions isolated of Laurel to control adults and larvae of cattle ticks

Abstract

This study, was to evaluate the acaricidal effect of the essential oil (EO) and fractions (FR) obtained from Laurus nobilis leaves on Rhipicephalus (Boophilus) microplus. Eight fractions were obtained, however FR1: sabinene (37.83%), β-pinene (13.50%), 1,8-cineole (12.66%), α-pinene (12.56%) and FR8: α-terpineol (79.19%) were highlighted as to the larvicidal potential when submitted by Larval Packet Test. The EO was tested by the Adult Immersion Test, at concentrations of 200.00; 100.00 and 50.00?µL/mL caused mortality of engorged females, egg mass reduction and hatching inhibition. Two fractions are shown to be efficient in controlling larvae FR8 (LC₅₀?=?0.13?µL/mL, LC₉₉?=?0.51?µL/mL) and FR1 (LC₅₀?=?0.20?µL/mL, LC₉₉?=?0.56?µL/mL). The fractionation of EO was determinant to elucidate which compounds were responsible for the larvicidal potential. This study opens new perspectives to direct new bioassays with the compounds obtained in the fractionation, since they present high potential on cattle tick larvae.