Simultaneous determination of erlotinib and its isomeric major metabolites in human plasma using isocratic liquid chromatography–tandem mass spectrometry and its clinical application

This study developed a method for the simultaneous determination of erlotinib and its isomeric major metabolites, OSI‐413 and OSI‐420, in human plasma using an isocratic liquid chromatography–tandem mass spectrometry. Plasma specimens deproteinized with acetonitrile were separated using a 3‐µm particle size octadecylsilyl column. The m/z values of the precursor and product ions for the analytes were as follows: erlotinib, 394.2/278.2; and OSI‐413 and OSI‐420, 380.2/278.2. The total run time was 21 min and no peaks interfering with the analytes and internal standard (d₆‐erlotinib) in human plasma were observed. The calibration curves of erlotinib, OSI‐413 and OSI‐420 were linear over the concentration ranges of 10–3000, 2–500 and 2–100 ng/mL, respectively. The pretreatment recovery ratios were >86.1%. The intra‐ and inter‐assay precisions and accuracies were <12.7 and 89.0–108.9% for all analytes. This validated method was applied to the determination of plasma samples in lung cancer patients receiving 150 mg of oral erlotinib. The plasma concentration ranges of erlotinib, OSI‐413 and OSI‐420 were 373–2354, 15.7–379 and 2.5–43.6 ng/mL, respectively. In conclusion, the present method can be helpful for evaluating the plasma exposures of erlotinib and its major isomeric metabolites in clinical settings. Copyright © 2014 John Wiley & Sons, Ltd.     

Relativistic Lagrangians for the Lorentz–Dirac equation

We present two types of relativistic Lagrangians for the Lorentz–Dirac equation written in terms of an arbitrary world-line parameter. One of the Lagrangians contains an exponential damping function of the proper time and explicitly depends on the world-line parameter. Another Lagrangian includes additional cross-terms consisting of auxiliary dynamical variables and does not depend explicitly on the world-line parameter. We demonstrate that both the Lagrangians actually yield the Lorentz–Dirac equation with a source-like term.     

Synthesis and dynamic structure of multinuclear Rh complexes of porphyrinoids

Large porphyrinoids with three Rh(CO)2 groups at their dipyrrin units shows two-step metal transposition through the macrocycle in solution and the equilibrium between the C3v-isomer and the Cs-isomer depends on the solvent polarity.     

Highly soluble [1]benzothieno[3,2-b]benzothiophene (BTBT) derivatives for high-performance, solution-processed organic field-effect transistors

2,7-Dialkyl[1]benzothieno[3,2-b]benzothiophenes were tested as solution-processible molecular semiconductors. Thin films of the organic semiconductors deposited on Si/SiO2 substrates by spin coating have well-ordered structures as confirmed by XRD analysis. Evaluations of the devices under ambient conditions showed typical p-channel FET responses with the field-effect mobility higher than 1.0 cm2 V-1 s-1 and Ion/Ioff of approximately 10(7).     

Anionic Sublattices in Halide Solid Electrolytes: A Case Study with the High-Pressure Phase of Li3ScCl6

The Li₃MX₆ compounds (M=Sc, Y, In; X=Cl, Br) are known as promising ionic conductors due to their compatibility with typical metal oxide cathode materials. In this study, we have successfully synthesized γ-Li₃ScCl₆ using high pressure for the first time in this family. Structural analysis revealed that the high-pressure polymorph crystallizes in the polar and chiral space group P6₃mc with hexagonal close-packing (hcp) of anions, unlike the ambient-pressure α-Li₃ScCl₆ and its spinel analog with cubic closed packing (ccp) of anions. Investigation of the known Li₃MX₆ family further revealed that the cation/anion radius ratio, r_M/r_X, is the factor that determines which anion sublattice is formed and that in γ-Li₃ScCl₆, the difference in compressibility between Sc and Cl exceeds the ccp r_M/r_X threshold under pressure, enabling the ccp-to-hcp conversion. Electrochemical tests of γ-Li₃ScCl₆ demonstrate improved electrochemical reduction stability. These findings open up new avenues and design principles for lithium solid electrolytes, enabling routes for materials exploration and tuning electrochemical stability without compositional changes or the use of coatings.     

Toward uniform polymer architecture through stereospecific living polymerization and chromatographic separation technique

Isotactic (it-) and syndiotactic (st-) poly(methyl methacrylate)s (PMMAs) were fractionated into uniform PMMAs (without molecular weight distribution) by supercritical fluid chromatography (SFC). The SFC technique was applied to the isolation of uniform it- and st-PMMAs with a hydroxy group (it- and st-PMMA-OH) at the chain end. Equimolar amounts of uniform it- and st-PMMA-OHs were coupled with sebacoyl dichloride to form uniform stereoblock PMMA. The reaction of uniform st-PMMA-OH with methacryloyl chloride gave uniform PMMA macromonomer with methacryloyl group at the chain end. The resulting uniform macromonomer was polymerized radically and the products were fractionated into uniform comblike polymers (1mer to 4mer) by means of gel-permeation chromatography (GPC). The uniform st-PMMA-OH was reacted with 1, 3, 5-benzenetricarbonyl trichloride to form uniform st-tri-armed star polymer. Some of the properties of these uniform stereoregular polymer architectures were studied.