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.     

On diquark clustering in quark—gluon plasma

The possibility that pairs of quarks will form diquark clusters in the regime above deconfinement transition for hadron matter at finite density is revisited. Here we present the results on the diquark-diquark (dq-dq) interaction in the framework of constituent quark model taking account of spin, isospin and color degrees of freedom in the spirit of generalized Pauli principle. By constructing the appropriate spin and color states of the dq-dq clusters we compute the expectation values of the interaction Hamiltonian involving pairwise quark—quark interaction. We find that the effective interaction between two diquark clusters is quite sensitive to different configurations characterized by color and spin states, obtained after the coupling of two diquark states. The value of the coupling parameter for a particular color—spin state, i.e., -3, 1 is compared to the one obtained earlier by Donoghue and Sateesh,Phys. Rev. D38, 360 (1988) based on the effective Φ⁴-theory. This new value of λ derived for different color-spin dq-dq states, may lead to several important implications in the studies of diquark star and diquark gas.     

A microspectroscopic study of the electronic homogeneity of ordered and disordered Sr2FeMoO6

Disordered Sr₂FeMoO₆ shows a drastic reduction in saturation magnetization compared to highly ordered samples, moreover magnetization as a function of the temperature for different disordered samples shows qualitatively different behaviours. We investigate the origin of such diversity by performing spatially resolved photoemission spectroscopy on various disordered samples. Our results establish that e_xtensive electronic inhomogeneity, arising most probably from an underlying chemical inhomogeneity in disordered samples, is responsible for the observed magnetic inhomogeneity. It is further pointed out that these inhomogeneities are connected with composition fluctuations of the type Sr₂Fe_1+x Mo_1-x O₆ with Fe-rich (x > 0) and Mo-rich (x < 0) regions. Dedicated to Prof J Gopalakrishnan on his 62nd birthday.     

Magnetism and magneto-transport studies in sonochemically prepared amorphous Co100−xPtx nano alloys

Bulk amorphous Co_(100−x)Pt_x (0≤x≤50) nano-alloys have been synthesized using high frequency ultrasound, displaying single domain (4-5 nm) behavior wherein weakly exchange-coupled particles lead to a field-dependent resistivity behavior. Magneto-resistivity is correlated to the order-disorder parameter in these powder compacts. The plot of Δρ/ρ₀ as a function of reduced magnetization indicates that all the systems are weakly exchange coupled.     

Azine bridged silver coordination polymers: Powder X-ray diffraction route to crystal structure determination of silver benzotriazole

In continuation of our interest in solid-state structures of silver complexes of photographic importance, the structure for silver benzotriazole (AgBZT), has now been obtained. The preferred method for solving crystal structures is via single-crystal X-ray diffraction (XRD). However, for some materials, growing single crystals of appropriate size and quality is often difficult or even impossible. AgBZT is an example of such a silver complex with poor solubility. The usual routes to preparing single crystals using recrystallization from a cooperating solvent resulted in polycrystalline powder samples. We propose a crystal structure for AgBZT, solved from synchrotron X-ray powder diffraction data, using a direct-space Monte Carlo simulated annealing approach. AgBZT crystals are monoclinic, (P2₁/c), with unit cell dimensions, a=14.8052(3) Å, b=3.7498(4) Å, c=12.3495(12) Å, and β=114.200(6)°. The AgBZT complex is constructed from all three of the Benzotriazole (BZT) nitrogens bonding to a separate silver atom. As a consequence of this bonding mode, the structure is a highly cross-linked, coordination polymer.     

Use of zirconium(IV) and antimony(III) for structural investigation of flavonoids

Summary The absorption spectra (in the visible and ultraviolet) of the complexes formed in absolute methanol between Zr⁴⁺, V⁴⁺, Y³⁺ and Sb³⁺ with 3-hydroxyflavone, apigenin, hesperidin, naringenin, morin, kaempferol, quercetin, rutin and myricetin have been studied. Zr⁴⁺ and Sb³⁺ form complexes that are stable in acid medium. The stoichiometry of the vairous Zr⁴⁺-flavonoid complexes formed in methanol and methanol/HClO₄ media has been determined by the molar ratio method. The preferred sites for complex formation of flavonoids with Zr⁴⁺ are postulated. Zr⁴⁺ forms chelates with the 3-hydroxy-4-keto and 5-hydroxy-4-keto systems simultaneously. Sb³⁺ forms complexes only with the 3,5-dihydroxy system in flavonoids. The results permit estimation of the relative order of chelating power of each type of binding site and are useful in elucidation of the structure of the flavonoids.

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Verwendung von Zirkonium(III) und Antimon(III) für die Erforschung der Flavonoide

Zusammenfassung Die Absorptions-Spektren (im sichtbaren und UV-Bereich) der in absolutem Methanol hergestellten Komplexe von Zr⁴⁺, V⁴⁺, Y³⁺ und Sb³⁺ mit 3-Hydroxyflavon, Apigenin, Hesperidin, Naringenin, Morin, Kaempferol, Quercetin, Rutin und Myricetin wurden untersucht. Zr⁴⁺ und Sb³⁺ bilden in saurem Milieu beständige Komplexe. Die Stöchiometrie der verschiedenen Zr⁴⁺-Flavonoid-Komplexe, die in Methanol bzw. Methanol/ HClO₄ hergestellt wurden, wurde durch Bestimmung der Molarverhältnisse ermittelt. Die für die Komplexbildung bevorzugten Stellen (im Molekül) wurden angegeben. Zr⁴⁺ bildet Chelate mit der 3-Hydroxy-4-keto- und mit der 5-Hydroxy~4-ketogruppe. Sb³⁺ bildet solche Komplexe nur mit der 3,5-Dihydroxy-4-keto-Gruppe in Flavonoiden. Die Untersuchungsergebnisse ermöglichen die Abschätzung der Komplexbildungsfähigkeit der verschiedenen Gruppierungen und sind für die Strukturaufklärung von Nutzen.

     

Steric effects of substituted quinolines on lithium coordination geometry

The X-ray crystal structures of a series of lithium quinolates – lithium 8-hydroxyquinolinate (Liq), lithium 2-methyl-8-hydroxyquinolinate (MeLiq), and 2-phenyl-8-hydroxquinolinate (PhLiq), are compared. The substitution at the 2-position of the 8-hydroxyquinoline ligand has significant impact on the aggregation of the lithium complex in the crystalline state. Liq and MeLiq molecules crystallize as hexamers, whereas PhLiq crystallizes as a tetramer. The possible influence of crystal-packing forces on the preferred cluster structure was probed using density functional theory calculations on a systematically varied set of Liq, MeLiq, and PhLiq clusters. For Liq and MeLiq, the observed structures match the most stable computed structures. In the PhLiq case, the observed tetrameric structure is computed to be less stable (+1.2 kcal/mol/monomer) than the lowest energy structure, a hexamer. In this case, solid-state effects probably outweigh small differences in cluster stability.     

Optimization of experimental parameters in single-drop microextraction-gas chromatography-mass spectrometry for the determination of periodate by the Malaprade reaction, and its application to ethylene glycol

The aim of present work was to optimize the experimental parameters in single drop microextraction under solution immersion (SDME) and headspace (HS-SDME) extraction modes for the determination of periodate using guaifenesine [3-(2′-methoxyphenoxy)-1,2-propane diol] and norephedrine (phenylpropanolamine) as new and alternative reagents for the Malaprade reaction. The reactions were complete within 5 min resulting in the formation of 2-(2′-methoxyphenoxy)-acetaldehyde and benzaldehyde, respectively. SDME/HS-SDME of oxidation products with 2 μl of anisole or 1 μl of toluene, respectively, has permitted the determination of periodate at μg l⁻¹ concentration levels. The results indicated that HS-SDME (range 0.01-10 mg l⁻¹, r² = 0.9990; limit of detection 1.55 μg l⁻¹) was more sensitive than SDME (range 0.05-50 mg l⁻¹, r² = 0.9984; limit of detection 3.42 μg l⁻¹), and was inexpensive, rapid and convenient. Tolerance of excess of iodate has permitted the application of this method in the determination of ethylene glycol in motor oil; the average recovery on spiked sample was 98.6% with R.S.D. of 4.2%.