A dried blood spot assay with HPLC–MS/MS for the determination of larotrectinib in mouse blood and its application to a pharmacokinetic study

Larotrectinib is a first-generation tropomyosin kinase inhibitor, approved for the treatment of solid tumors. In this paper, we present a validated dried blood spot (DBS) method for the quantitation of larotrectinib from mouse blood using HPLC–MS/MS, which was operated under multiple reaction monitoring mode. To the DBS disc cards, acidified methanol enriched with internal standard (IS; enasidenib) was added and extracted using tert-butyl methyl ether as an extraction solvent with sonication. Chromatographic separation of larotrectinib and the IS was achieved on an Atlantis dC₁₈ column using 10 mm ammonium formate–acetonitrile (30:70, v/v) delivered at a flow-rate of 0.80 ml/min. Under these optimized conditions, the retention times of larotrectinib and the IS were ~0.93 and 1.37 min, respectively. The total run time was 2.50 min. Larotrectinib and the IS were analyzed using positive ion scan mode and parent–daughter mass to charge ion (m/z) transitions of 429.1 → 342.1 and 474.1 → 267.1, respectively, were used for the quantitation. The calibration range was 1.06–5,080 ng/ml. No matrix effect or carryover was observed. Hematocrit did not influence DBS larotrectinib concentrations. All of the validation parameters met the acceptance criteria. The applicability of the validated method was shown in a mouse pharmacokinetic study.     

An EOQ model with process reliability considerations

The classical economic order quantity (EOQ) model assumes that items produced are of perfect quality and that the unit cost of production is independent of demand. However, in realistic situations, product quality is never perfect, but is directly affected by the reliability of the production process. In this paper, we consider an EOQ model with imperfect production process and the unit production cost is directly related to process reliability and inversely related to the demand rate. In addition, a numerical example is given to illustrate the developed model. Sensitivity analysis is also performed and discussed.     

Transition of 3D to 2D growth modes of InAs grown on GaAs

We report a method to grow thin strain-released InAs layer on GaAs (1 0 0) substrates by molecular beam epitaxy. We have shown that by controlling the growth parameters, a thin 2D InAs layer can be grown during initial stages, which eventually serves as a buffer layer to trap dislocations and epitaxial regrowth of InAs on this buffer results in high crystal quality. The size dependence of the InAs islands formed during initial stages with growth time has been studied by atomic force microscopy. With continuous short-time epitaxial growth during various stages, the InAs growth mode transfers from 3D to 2D. The introduction of dislocations into InAs epitaxial islands and their behavior during initial growth stage has been theoretically studied. The theoretical results are in remarkable agreement with the experimental results and shows that once the film is formed, the film strain is totally relaxed. The 200 nm thick InAs epilayer grown on this buffer shows a narrow X-ray diffraction peak. Such InAs strain-released buffer layer would be useful for regrowth of high In content based materials on top of it for electronics and optoelectronics device applications.     

Working group report: Flavor physics and model building

This is the report of flavor physics and model building working group at WHEPP-9. While activites in flavor physics have been mainly focused on B-physics, those in model building have been primarily devoted to neutrino physics. We present summary of working group discussions carried out during the workshop in the above fields, and also briefly review the progress made in some projects subsequently.     

Substituted m-phenylene bridges as strong ferromagnetic couplers for Cu(II)-bridge-Cu(II) magnetic interactions: new perspectives

Based on a combined theoretical-experimental study, we propose that substituted m-phenylene ligands (m-N-Phi-N) can act as tuneable strong ferromagnetic couplers connecting Cu(II) ions; a new complex presenting that bridge with J close to +15 cm(-1) has been suggested and synthesized.     

Reductive nitrosylation of tetraoxometallates—XVII. Molybdate-hydroxylamine-cyanide reaction, and synthesis and characterization of K2[Mo(NO)(CN)5] and (NMe4)2[Mo(NO)(CN)4]

A reaction condition is established which determines the nature of the products in the molybdate-hydroxylamine-cyanide reaction. With hydroxylamine always used in excess, it is the hydroxyl ion concentration of the reaction mixture which plays a vital role in determining whether K₄[Mo(NO)(CN)₅] or K₂[Mo(NO)(CN)₅] is obtained exclusively. The latter product is hereby reported for the first time. Its powder diffractogram being typical of a cubic system, a gross structural characterization has been made possible. The former under aqueous, aerobic conditions yields a new product, (NMe₄)₂[Mo(NO)(CN)₄].     

A general microcantilever surface modification method using a multilayer for biospecific recognition

The key to microcantilever surface modification technology is to selectively modify one side of a microcantilever surface with molecular recognition layers. In this paper, we report a general microcantilever modification method using a multilayer film.     

Extracellular pH influences the mode of cell death in human colon adenocarcinoma cells subjected to photodynamic treatment with chlorin p6

Effect of varying extracellular pH on mode of cell death induced by photodynamic action of chlorin p6 was investigated in human colon carcinoma (Colo-205) cells. At an extracellular pH of 7.4, compared to cells treated with chlorin p6 in dark, the photodynamically treated cells showed reduction in mitochondrial membrane potential, an increase in ADP/ATP ratio (1:2) and a large percentage of cells with chromatin condensation. In contrast, when photodynamic treatment and post irradiation incubation was carried out in acidic medium (pH 6.5), total loss of mitochondrial membrane potential, a marked increase in ADP/ATP ratio (1:33) and increased damage to plasma membrane were observed. Further, cells subjected to photodynamic treatment in a medium of pH 7.4 showed twofold increase in caspase-3 activity as compared to photodynamic treatment at pH 6.5. These results suggest that chlorin p6 mediated photodynamic action induces apoptotic cell death when extracellular pH is 7.4 whereas necrosis is more predominant under condition when extracellular pH is 6.5.     

Fabrication of nanoscale metallic spirals using phospholipid microtubule organizational templates

We describe the fabrication of metallic Cu spiral/helical nanostructures prepared via selective electroless metallization of a phospholipid microtubule template. The metallization template is created through selective, sequential adsorption of the oppositely charged polyelectrolytes, sodium poly(styrenesulfonate) (PSS) and poly(ethyleneimine) (PEI), onto nanoscale seams naturally occurring on the microtubule surface. A negatively charged Pd(II) nanoparticle catalyst is bound to the terminal cationic PEI layer of the multilayer film and initiates selective template metallization to form the helical Cu nanostructures. Details of the process are presented, and a mechanism and factors affecting the control of the feature critical dimensions are discussed.     

Thermochromism in nickel(II) complexes: thermal, solid state H NMR and single crystal X-ray analysis of bis-(N,N-dimethyl-1,2-ethanediamine) nickel(II) perchlorate

The complex bis-(N,N-dimethyl-1,2-ethanediamine) nickel(II) perchlorate undergoes a first-order thermochromic phase transition at ca. 476 K, changing its color from orange to red. The room temperature X-ray crystal structure determination showed that the nickel ion possesses a square-planar geometry with two five membered chelate rings, in the δλ conformation, forming the NiN₄ chromophore. The broad-line ¹H NMR indicates the onset of a dynamic disorder of diamine chelate rings at the phase transition temperature region, while T₁ measurement of ¹H affords the activation energy of the puckering metal chelate rings to be 26 kJ mol⁻¹. The electronic spectrum revealed that a weakening of ligand field around the nickel is associated with the phase transition.