Validated LC–MS/MS method for quantitation of a selective JAK1 inhibitor,filgotinib in rat plasma,and its application to a pharmacokinetic study in rats

Filgotinib is a selective JAK1 (Janus kinase) inhibitor, filed in Japan for the treatment of rheumatoid arthritis. In this paper, we report a validated liquid chromatography coupled with tandem mass spectrometry for the quantification of filgotinib in rat plasma using tofacitinib as an internal standard (IS) as per the Food and Drug Administration regulatory guidelines. Filgotinib and the IS were extracted from rat plasma using ethyl acetate as an extraction solvent and chromatographed using an isocratic mobile phase (0.2% formic acid:acetonitrile; 20:80, v/v) at a flow rate of 0.9 mL/min on a Gemini C₁₈ column. Filgotinib and the IS were eluted at ~1.31 and 0.89 min, respectively. The MS/MS ion transitions monitored were m/z 426.3 → 291.3 and m/z 313.2 → 149.2 for filgotinib and the IS, respectively. The calibration range was 0.78–1924 ng/mL. No matrix effect and carryover were observed. Intra- and inter-day accuracies and precisions were within the acceptance range. Filgotinib was stable for three freeze–thaw cycles: on bench-top up to 6 h, in an autosampler up to 21 h, and at −80 ° C for 1 month. This novel method has been applied to a pharmacokinetic study in rats.     

Enantioselective LC–ESI–MS/MS method for quantitation of (−)-lumefantrine and (+)-lumefantrine in mice plasma and application to a pharmacokinetic study

We developed and validated a simple, sensitive, selective, and reliable LC–MS/MS–ESI method for the direct quantitation of lumefantrine (LFN) enantiomers [(−)-LFN and (+)-LFN] in mice plasma as per regulatory guideline. LFN enantiomers and carbamazepine (internal standard) were extracted from mice plasma using Strata X SPE (solid-phase extraction) cartridges. Good resolution between enantiomers was achieved on a Chiralpak IA-3 column using an isocratic mobile phase (0.1% of diethyl amine in methanol), which was delivered at a flow rate of 0.8 mL/min. Detection and quantitation were performed using multiple reaction monitoring mode following the transitions m/z 530.27 → 512.30 and 237.00 → 194.00 for LFN enantiomers and the internal standard, respectively, in the positive-ionization mode. The proposed method provided accurate and reproducible results over the linearity range of 2.39–895 ng/mL for each enantiomer. The intra- and inter-day precisions were in the range of 1.03–6.14 and 6.36–8.70 and 2.03–4.88 and 5.82–11.5 for (−)-LFN and (+)-LFN, respectively. Both (−)-LFN and (+)-LFN were found to be stable under different stability conditions. The method was successfully used to delineate stereoselective pharmacokinetics of LFN enantiomers in mice after an oral administration of rac-LFN (20 mg/kg). The pharmacokinetic results indicated that the disposition of LFN enantiomers was stereoselective in mice.     

Structural and thermal studies of [PVA–LiAc] : TiO2 polymer nanocomposite system

Nanocomposite polymer electrolyte consisting of polyvinyl alcohol (PVA) and lithium acetate with TiO₂ filler has been synthesised by combination of solution cast technique and sol–gel process. The composite electrolyte films were characterised by different experimental techniques. The average particle size of composite electrolytes lies between 25 and 30?nm. System is essentially ionic with maximum conductivity of polymer electrolyte 90[80PVA–20LiAc]:10TiO₂ (～4.5?×?10^?6?S?cm^?1) at room temperature.     

Quantitative Analysis by Derivative Electronic Spectroscopy

Abstract

Absorption and emission spectroscopy in the ultraviolet and visible regions, apart from being the earliest physical techniques of analysis, have great utility in solving a variety of structural and analytical problems [l-41. However, in many cases the quantitative determination of individual components in a mixture by UV-VIS spectroscopy becomes very difficult owing to the spectral similarities and overlapping of weak absorption bands of one component by strong absorption bands of other components. It was recently recognized that derivative spectrophotometry, introduced about three decades ago [5-81 and originally proposed by Rutherford [9], can be a very useful analytical tool for characterizing an analyte band that is overlapped by other absorption bands with different halfwidths. On differentiation, the intensity of the absorption band with a small halfwidth increases more than that of a band with a large halfwidth [10]. The central idea behind the development of the science of derivatized spectra rests upon the measurement of the first or the higher derivatives of the absorbance A or the luminescence intensity I with respect to the wavelength λ, e.g., dI/dλ, dA/dλ, d²I/dλ², etc. These derivatives, when plotted or scanned against wavelength, yield an array of derivative spectra.     

Swift heavy ion-induced effects in Ce-doped nickel ferrite nanoparticles

Swift heavy ions of various energies are being used for material modifications. The induced modifications depend on the kind of defects produced during interaction of ions with the target material. In the present work, irradiation of 200 MeV Ag beam-induced effects in NiFe₂O₄ and NiCe_0.04Fe_1.96O₄ nanoparticles are studied at two different fluences, 2×10¹² and 1×10¹³ ions/cm². Nanoparticles of nickel ferrite and Ce-doped nickel ferrite were prepared by chemical route. X-ray diffraction pattern shows peaks corresponding to pure spinel structure in both the systems, NiFe₂O₄ and NiCe_0.04Fe_1.96O₄. The pristine as well as irradiated nanoparticles were characterized by high-resolution transmission electron microscopy (HRTEM), Raman spectroscopy, electron paramagnetic resonance spectroscopy (EPR) and vibrating sample magnetometer (VSM). Raman spectra show bands corresponding to spinel structure. After irradiation, the position of the bands does not change significantly for both samples. The widths corresponding to the same band in both the systems show opposite trend with fluence. VSM results show that after irradiation, the magnetization decreases from 40 to 32 A m²/kg for NiFe₂O₄ and from 39 to 31 A m²/kg for NiCe_0.04Fe_1.96O₄. EPR results show that after doping with Ce as well as irradiation, the EPR line width is reduced, making samples important for applications.     

X-Ray fluorescence determination of Sm, Eu, Tb, Dy, Ho, Yb and Y in high purity gadolinium oxide

Summary An X-ray fluorescence method is described for the determination of Sm, Eu, Tb, Dy, Ho, Yb and Y in gadolinium oxide. Samples are taken in oxalate form and mixed with boric acid in the ratio 31. The mixture is pressed as a double-layer pellet. Selection of experimental parameters and choice of analysis lines is discussed. The estimation limit ranges from 0.005–1% for most of the elements.

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Röntgenfluorescenz-spektrometrische Bestimmung von Sm, Eu, Tb, Dy, Ho, Yb und Y in hochreinem Gadoliniumoxid

Zusammenfassung Bei dem vorgeschlagenen Verfahren werden die Proben in die Oxalatform übergeführt und mit Borsäure im Verhältnis 31 gemischt. Die Mischung wird zu einer Doppelschicht-Tablette gepreßt. Die Auswahl der geeigneten experimentellen Parameter sowie der Analysenlinien wird diskutiert. Die Bestimmungs-grenzen liegen für die meisten Elemente im Bereich 0,005–1%.