Enantioselective LC‐ESI‐MS/MS determination of dropropizine enantiomers in rat plasma and application to a pharmacokinetic study

We developed and validated a simple, sensitive, selective and reliable LC–ESI‐MS/MS method for direct quantitation of dropropizine enantiomers namely levodropropizine (LDP) and dextrodropropizine (DDP) in rat plasma without the need for derivatization as per regulatory guidelines. Dropropizine enantiomers and carbamazepine (internal standard) were extracted from 50 μL rat plasma using ethyl acetate. LDP and DDP resolved with good baseline separation (R_s = 4.45) on a Chiralpak IG‐3 column. The mobile phase consisted of methanol with 0.05% diethylamine pumped at a flow rate of 0.5 mL/min. Detection and quantitation were done in multiple reaction monitoring mode following the transitions m/z 237 → 160 and 237 → 194 for dropropizine enantiomers and the internal standard, respectively, in the positive ionization mode. The proposed method provided accurate and reproducible results over the linearity range of 3.23–2022 ng/mL for each enantiomer. The intra‐ and inter‐day precisions were in the ranges of 3.38–13.6 and 5.11–13.8 for LDP and 4.19–11.8 and 8.89–10.1 for DDP. Both LDP and DDP were found to be stable under different stability conditions. The method was successfully used in a stereoselective pharmacokinetic study of dropropizine enantiomers in rats following oral administration of racemate dropropizine at 100 mg/kg. The pharmacokinetic results indicate that the disposition of dropropizine enantiomers is not stereoselective and chiral inversion does not occur in rats.     

Quantitative analysis of enasidenib in dried blood spots of mouse blood using an increased‐sensitivity LC–MS/MS method: Application to a pharmacokinetic study

A simple, sensitive and rapid assay method has been developed and validated as per regulatory guidelines for the estimation of enasidenib on mouse dried blood spots (DBS) using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in the positive‐ion mode. The method employs liquid extraction of enasidenib from DBS disks of mouse whole blood followed by chromatographic separation using 0.2% formic acid–acetonitrile (25:75, v/v) at a flow rate of 1.0 mL/min on an Atlantis dC₁₈ column with a total run time of 2.0 min. The MS/MS ion transitions monitored were m/z 474.0 → 267.1 for enasidenib and m/z 309.2 → 251.3 for the internal standard (warfarin). The assay was linear in the range of 1.01 – 3044 ng/mL. The within‐run and between‐run precisions were in the range of 3.18 – 9.06 and 4.66 – 8.69%, respectively. Stability studies showed that enasidenib was stable on DBS cards for 1 month. This novel method has been applied to analyze the DBS samples of enasidenib obtained from a pharmacokinetic study in mice.     

A new procedure for the spectrophotometric determination of uranium(VI) in the presence of a large excess of thorium(IV).

Spectrophotometric determination of microgram amounts of U(VI) with 2-(5-Bromo-2-Pyridylazo)-5-diethylaminophenol (Br-PADAP), originally developed by Johnson and Florence has been modified to enable the determination of U(VI) in the presence of a large excess of Th(IV). The effects of thorium, tri-n-butyl phosphate (TBP) and ethanol on the estimation of uranium have been studied in detail and are presented in this paper. This modified method can be applied for the analysis of U(VI) both in aqueous and organic samples containing a large excess of Th(IV) (Th:U = 10000:1).     

Development and validation of an LC-MS/MS-ESI method for the determination of lorglumide, a CCK-1 antagonist in mouse plasma: application to a pharmacokinetic study

A highly sensitive, rapid assay method was developed and validated for the estimation of lorglumide in mouse plasma using liquid chromatography coupled to tandem mass spectrometry with electrospray ionization in positive‐ion mode. The assay procedure involves extraction of lorglumide and phenacetin (internal standard, IS) from mouse plasma with simple protein precipitation. Chromatographic separation was achieved using an isocratic mobile (0.2% formic acid solution–acetonitrile, 20:80, v/v) at a flow‐rate of 0.5 mL/min on an Atlantis dC₁₈ column maintained at 40 °C with a total run time of 4.0 min. The MS/MS ion transitions monitored were 459.2 → 158.4 for lorglumide and 180.1 → 110.1 for IS. Method validation was performed as per FDA guidelines and the results met the acceptance criteria. The lower limit of quantitation achieved was 0.42 ng/mL and the linearity range extended from 0.42 to 500 ng/mL. The intra‐ and inter‐day precisions were in the ranges of 1.47–10.9 and 3.56–7.53, respectively. Copyright © 2011 John Wiley & Sons, Ltd.     

A sensitive LC‐MS/MS method for the quantification of febuxostat in human plasma and its pharmacokinetic application

An improved, simple and highly sensitive LC‐MS/MS method has been developed and validated for quantification of febuxostat with 100 μL human plasma using febuxostat‐d₇ as an internal standard (IS) according to regulatory guidelines. The analyte and IS were extracted from human plasma via liquid–liquid extraction using diethyl ether. The chromatographic separation was achieved on a Zorbax C₁₈ column using a mixture of acetonitrile and 5 mm ammonium formate (60:40, v/v) as the mobile phase at a flow rate of 0.5 mL/min. The total run time was 5.0 min and the elution of febuxostat and IS occurred at 1.0 and 1.5 min, respectively. A linear response function was established for the range of concentrations 1–6000 ng/mL (r > 0.99). The precursor to product ion transitions monitored for febuxostat and IS were m/z 317.1 → 261.1 and 324.2 → 262.1, respectively. The intra‐ and inter‐day precisions (%RSD) were within 1.29–9.19 and 2.85–7.69%, respectively. The proposed method was successfully applied to pharmacokinetic studies in humans. Copyright © 2013 John Wiley & Sons, Ltd.     

Fast Reductive Amination by Transfer Hydrogenation “on Water”

Reductive amination of various ketones and aldehydes by transfer hydrogenation under aqueous conditions has been developed, by using cyclometallated iridium complexes as catalysts and formate as hydrogen source. The pH value of the solution is shown to be critical for a high catalytic chemoselectivity and activity, with the best pH value being 4.8. In comparison with that in organic solvents, the reductive amination in an aqueous phase is faster, and the molar ratio of the substrate to the catalyst (S/C) can be set as high as 1×10⁵, the highest S/C value ever reported in reductive amination reactions. The catalyst is easy to access and the reaction is operationally simple, allowing a wide range of ketones and aldehydes to react with various amines in high yields. The protocol provides a practical and environmental friendly new method for the synthesis of amine compounds.     

Regioselective Photocyclization Reactions of 3‐Allyloxy‐6‐chloro‐2‐(thiophen‐3‐yl)‐4H‐chromen‐4‐one: Solvent Effect

The photo‐irradiation of thienylchromenone resulted in the regioselective cyclization which is exclusively controlled by the nature of solvent used as reaction medium. Compared to nonpolar medium, polar solvent furnished a diverse array of novel angular tetracyclic photoproducts with gem‐dihydro functionality and exocyclic double bonds on the fused pyran ring, which is unprecedented to best of our knowledge.     

A Ferroelectric Aminophosphonium Cyanoferrate with a Large Electrostrictive Coefficient as a Piezoelectric Nanogenerator

Hybrid materials possessing piezo- and ferroelectric properties emerge as excellent alternatives to conventional piezoceramics due to their merits of facile synthesis, lightweight nature, ease of fabrication and mechanical flexibility. Inspired by the structural stability of aminophosphonium compounds, here we report the first A₃BX₆ type cyanometallate [Ph₂(ⁱPrNH)₂P]₃[Fe(CN)₆] ( 1 ), which shows a ferroelectric saturation polarization (P_s) of 3.71 μC cm⁻². Compound 1 exhibits a high electrostrictive coefficient (Q₃₃) of 0.73 m⁴ C⁻², far exceeding those of piezoceramics (0.034–0.096 m⁴ C⁻²). Piezoresponse force microscopy (PFM) analysis demonstrates the polarization switching and domain structure of 1 further confirming its ferroelectric nature. Furthermore, thermoplastic polyurethane (TPU) polymer composite films of 1 were prepared and employed as piezoelectric nanogenerators. Notably, the 15 wt % 1 -TPU device gave a maximum output voltage of 13.57 V and a power density of 6.03 μW cm⁻².     

Electrode Materials for Desalination of Water via Capacitive Deionization

Recent years have seen the emergence of capacitive deionization (CDI) as a promising desalination technique for converting sea and wastewater into potable water, due to its energy efficiency and eco-friendly nature. However, its low salt removal capacity and parasitic reactions have limited its effectiveness. As a result, the development of porous carbon nanomaterials as electrode materials have been explored, while taking into account of material characteristics such as morphology, wettability, high conductivity, chemical robustness, cyclic stability, specific surface area, and ease of production. To tackle the parasitic reaction issue, membrane capacitive deionization (mCDI) was proposed which utilizes ion-exchange membranes coupled to the electrode. Fabrication techniques along with the experimental parameters used to evaluate the desalination performance of different materials are discussed in this review to provide an overview of improvements made for CDI and mCDI desalination purposes     

Kinetics and mechanism of the oxidation of 2-furancarbox-aldehyde by thallium(III) in perchloric acid solutions

The kinetics of the oxidation of 2-furancarboxaldehyde by thallic perchlorate at 50°C obeys the rate law