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.     

Synthesis and liquid crystalline properties of new amide‐modified poly(1,4‐cyclohexanedimethylene terephthalate)

New series of cycloaliphatic poly(ester‐amide)s, poly(1,4‐cyclohexanedimethyleneterephthalate‐co‐1,3‐cyclohexanedimethylene terephthalamide), were synthesized through solution polymerization route. The compositions of ester/amide units in the copolymers were varied from 0 to 100% by varying the amount of 1,4‐cyclohexanedimethanol and 1,3‐cyclohexanebis(methylamine) in the feed. The structures of the polymers were confirmed by NMR and FTIR, and the molecular weights were determined by inherent viscosity. The composition analysis by NMR reveals that the reactivity of the diamine toward the acid chlorides is lowered than that of diol, which results in the formation of more ester content in the poly (ester‐amides). The thermal analysis indicate that the new poly(ester‐amide)s having less than 10 mol % of amide linkages are thermotropic liquid crystalline from 200 to 250 °C and a thread like nematic phases are observed under the polarizing microscope. WXRD studies suggest that the liquid crystalline domains promote the nucleation process in the polyester chains and increases the percent crystallinity of the poly(ester‐amide)s. The glass transition temperature of the copolymers initially increases with increase in amide units because of the presence of nematic phases and subsequently follows the Flory–Fox behavior. © 2005 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 42–52, 2006     

Fouling and protein adsorption effect of low-temperature plasma treatment of membrane surfaces

Adsorption of proteins and the effect of the chemical nature of membrane surfaces on protein adsorption were investigated using¹⁴C-tagged albumin and several microporous membranes (polyvinilydene fluoride, PVDF; nylon; polypropylene, PP; and polycarbonate, PC). The membrane surfaces were modified by exposing them to low-temperature plasma of several different monomers (n-butane, oxygen, nitrogen alone or as mixtures) in a radiofrequency plasma reactor. Transients in the permeability of albumin solutions through the membranes and changes in flux of distilled water through the membranes before and after adsorption of albumin were used to investigate the role of protein adsorption on membrane fouling. The results show that the extent of adsorption of albumin on hydrophobic membranes was considerably more than that on hydrophilic membranes. The hydrophilic membranes were susceptible to electrostatic interactions and less prone to fouling. A pore-blocking model was successfully used to correlate the loss of water flux through pores of defined geometry     

Extraction of U(VI) by cyanex-272

Extraction of U(VI) from HNO₃, HCl and HClO₄ media using cyanex-272 (bis[2,4,4 trimethyl pentyl] phosphinic acid)/n-dodecane has been carried out. In the case of HNO₃ and HClO₄ media, the distribution ratio (D) value first decreases and then increases, whereas from HCl medium it first decreases and then remains constant with increase in H⁺ ion concentration. At lower acidities, U(VI) was extracted as UO₂(HA₂)₂ by an ion exchange mechanism, whereas at higher acidities as UO₂(NO₃)₂ ^.2(H₂A₂) following a solvation mechanism. The D for U(VI) by cyanex-272, PC-88A and DEHPA at low acidities follows the order cyanex-272 > PC-88A > DEHPA. Also, cyanex-272 was found to extract U(VI) more efficiently than TBP at 2M HNO₃. The effect of diluents on the extraction of U(VI) by cyanex-272 followed the order cyclohexane > n-dodecane > CCl₄ > benzene. The loading of U(VI) into cyanex-272/n-dodecane from 2M HNO₃ has shown that at saturation point, cyanex-272 was 78% loaded. No third phase was observed at the saturation level. The stripping of U(VI) from the loaded organic phase was not possible with water, it was poor with acetic acid and sodium acetate but quantitative with oxalic acid, ammonium carbonate and sodium carbonate.     

Combining synchronous fluorescence spectroscopy with multivariate methods for the analysis of petrol-kerosene mixtures

Synchronous fluorescence spectroscopy (SFS) is a rapid, sensitive and nondestructive method suitable for the analysis of multifluorophoric mixtures. The present study demonstrates the use of SFS and multivariate methods for the analysis of petroleum products which is a complex mixture of multiple fluorophores. Two multivariate techniques principal component regression (PCR) and partial least square regression (PLSR) have been successfully applied for the classification of petrol-kerosene mixtures. Calibration models were constructed using 35 samples and their validation was carried out with varying composition of petrol and kerosene in the calibration range. The results showed that the method could be used for the estimation of kerosene in kerosene-mixed petrol. The model was found to be sensitive, detecting even 1% contamination of kerosene in petrol.     

Tamarindus indica mucilage and its acrylamide-grafted copolymer as flocculants for removal of dyes

The application of Tamarindus indica seed mucilage (Tam), a food grade polysaccharide, and its acrylamide grafted copolymer as flocculants was assessed for the first time for removal of various types of dyes from model textile wastewater containing azo, basic, and reactive dyes. Acrylamide grafted T. indica mucilage (Tam-g-PAM) was obtained by ceric ion initiated polymerization technique. A series of contact time experiments were conducted to assess the system variables such as concentrations of mucilage and dyes and pH. These flocculants reduce the dye concentration by flocculation and settling. The grafted copolymer, Tam-g-PAM showed better results for dye removal. The optimal flocculant concentration, which was required to effect flocculation, was independent of dye concentration within the range examined. Both the flocculants performed better for removal of azo dyes than for reactive and basic dyes.     

A relaxation study of poled nonlinear optical polymers by infrared reflection-absorption spectroscopy

The relaxation of poled nonlinear optical (NLO) chromophores in polymer films was characterized by infrared (i.r.) reflection-absorption spectroscopy. Both a guest-host system and a photocrosslinkable polymer system were investigated. Polymethylmethacrylate doped with either 2-methyl-4-nitroaniline or 4(4′-nitrophenylazo)aniline was studied. The photocrosslinkable polymer system, polyvinylcinnamate doped with 3-cinnamoyloxy-4-[4-(N,N-diethylamino)-2-cinnamoyloxy phenyl azo]nitrobenzene was also investigated. Doped NLO active molecules were aligned using the corona poling technique. i.r. spectra as a function of time were used to monitor the relaxation behavior of the oriented dyes after poling. Relaxation of NLO molecules was followed at various characteristic vibrational frequencies. The relaxation behavior of both systems were found to be consistent with those studied by the second harmonic generation technique.     

Microhardness measurements of poly(methyl methacrylate) and poly(vinylidene fluoride) polyblends

The preparation of polymer blends of poly(methyl methacrylate) and poly(vinylidene fluoride) in different weight percentages is described. Vickers microhardness measurements have been made to study the effects of load and compositional ratio of the two polymers in polyblend. It is observed that poly(vinylidene fluoride) acts as a plasticizer for poly(methyl methacrylate). Evidence of increasing and decreasing strength of polyblends has been obtained for different compositional ratios of the two polymers.