Cycloparaphenylene (CPP) series are molecular models for graphene armchair edges: trends in their aromaticity and cyclic conjugation are evaluated

Cycloparaphenylene ([r]CPP) and cyclacene ([r]CA) series are models for short carbon nanotubes. It is shown that armchair edges in model cycloparaphenylenes possess greater aromaticity and cyclic conjugation than do zigzag edges in model cyclacenes. According to Aihara’s bond resonance energy (BRE) and Bosanac and Gutman energy effect (ef) measurements, cycloparaphenylenes are twice as aromatic as cyclacenes. The general solution of all eigenvalues of all members of the cycloparaphenylene series is given. The origin of the recurrence of some eigenvalues are determined.     

Sonication-Assisted Synthesis of Bimetallic Hg/Pd Alloy Nanoparticles for Catalytic Reduction of Nitrophenol and its Derivatives

In this article, we report a facile approach for the synthesis of an inexpensive catalyst of bimetallic Hg/Pd alloys comprising nanoparticles with various structures using a unique ultrasonic reaction that is conducted without the use of any reducing agent. The nanoparticles of Hg/Pd alloys (HgPd and Hg₂Pd₅) were achieved for the first time by sonicating an aqueous solution of Palladium (II) nitrate with metallic liquid mercury, as evidenced by XRD. EDS further confirmed the presence of Pd and Hg elements in the alloy. The surface morphology and structure of the nanoparticles have been systematically investigated by HRSEM, HRTEM and SAED pattern. In order to explore the catalytic activity of the as-synthesized nanoalloys, the catalytic reduction of 4-nitrophenol and a few other nitrophenol derivatives were investigated. Excellent catalytic activity was obtained for Hg/Pd (1:1) alloy, and the rate constant for the reduction of 4-NP with Hg/Pd at room temperature was found to be 58.4 × 10⁻³ s⁻¹, which is possibly the highest ever reported. The catalyst exhibited superior stability and reusability when compared with those reported in the literature for other catalysts based on noble metals.     

Proton conductivity study on three CS/IL@fle-MOF membranes

The low-cost, high specific surface area and porosity, controlled pore size, and chemical properties of metal–organic framework (MOF) materials have attracted much attention in the exploration of proton conduction. The method of chemically modifying MOF structures or introducing conductive medium into the holes can effectively improve the proton conductivities of the materials. Here, the structural tunability of ionic liquid (IL) and flexible MOF (fle-MOF) materials are matched to give full play to the conductivity of IL, the framework support, and the microporous effect of MOFs, which achieves the synergistic effect of performance and expands the temperature range of proton transfer. Three kinds of CS/IL@fle-MOF membranes were prepared by combining three fle-MOFs with 1-carboxymethyl-3-methylimidazole (CMMIM) in different proportions to obtain 15 pieces of membranes. The comparative analyses show that CS/IL@fle-MOF membranes have excellent proton conduction performance at a wider temperature range (263–353 K) and lower relative humidity (75% RH). Among them, the proton conductivities of CS/CMMIM@MIL-88A-25% and CS/CMMIM@MIL-88B-125% are up to 1.33 and 1.42 S cm⁻¹ at 75% RH and 353 K, respectively; whereas those of CS/CMMIM@MIL-53(Fe)-75% and CS/CMMIM@MIL-88B-125% reach up to 2.1 × 10⁻³ and 1.28 × 10⁻³ S cm⁻¹ at 75% RH and 263 K, respectively. The E_a of CS/CMMIM@fle-MOFs is in the range of 0.1–0.5 eV, suggesting that the proton transport follows predominantly the typical Grotthuss transfer mechanism. The results of this study indicate that the CS/CMMIM@fle-MOF membranes combinations offer great potential for the design of composite porous proton-conducting materials.     

A novel approach to the quantification of urinary aryl-propionamide-derived SARMs by UHPLC–MS/MS

A simple and sensitive procedure for the quantification of two commonly abused aryl-propionamide-derived selective androgen receptor modulators (SARMs), namely S-4 (GTx-007, andarine) and S-22 (GTx-024, MK-2866, ostarine, enobosarm), has been described. Urine samples were prepared for analysis by means of a dispersive liquid–liquid microextraction using methanol and chloroform as dispersive and extracting solvents, respectively. Factors that might influence the extraction process as well as their optimum conditions were evaluated by Box–Benken and central composite designs. After extraction, the analytes were quantified by UHPLC–MS/MS. The proposed procedure was validated on human urine samples. As a result, for both SARMs the detection limits were observed at 0.05 ng/mL and calibration curves were linear in the concentration range of 0.25–50 ng/mL with the coefficient of determination of 0.998.     

Quantification of fenoprofen in human plasma using UHPLC–tandem mass spectrometry for pharmacokinetic study in healthy subjects

A rapid, simple and sensitive ultra-performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method has been developed to quantify fenoprofen, a nonsteroidal anti-inflammatory drug in human plasma for a pharmacokinetic study in healthy subjects. Owing to high levels of protein binding, protein precipitation followed by solid-phase extraction was employed for the extraction of fenoprofen and fenoprofen-d3 (used as internal standard) from 200 μL human plasma. Separation was performed on a BEH C₁₈ (50 × 2.1 mm, 1.7 μm) column using methanol−0.2% acetic acid in water (75:25, v/v) under isocratic elution. Electrospray ionization was operated in the negative mode for sample ionization. Ion transitions used for quantification in the selected reaction monitoring mode were m/z 241/197 and m/z 244/200 for fenoprofen and fenoprofen-d3, respectively. Under the optimized conditions, fenoprofen showed excellent linearity in the concentration range 0.02–20 μg/mL (r² ≥ 0.9996), adequate sensitivity, favorable accuracy (96.4–103.7%) and precision (percentage coefficient of variation ≤4.3) with negligible matrix effect. The validated method was successfully applied to a pharmacokinetic study of fenoprofen in healthy subjects. The significant features of the method include higher sensitivity, small plasma volume for processing and a short analysis time.     

Quantification and pharmacokinetic property of verubecestat an BACE1 inhibitor in rat plasma

In the present study, an ultra-performance liquid chromatography tandem mass spectrometry (UPLC–MS/MS) approach was designed to measure the rat plasma levels of verubecestat with diazepam as the internal standard. Acetonitrile-based protein precipitation was applied for sample preparation, then the analyte verubecestat was subjected to gradient elution chromatography with a mobile phase composed of acetonitrile (A) and 0.1% formic acid in water (B). Verubecestat was monitored by m/z 410.1 → 124.0 transition for quantification by multiple reaction monitoring (MRM) in positive ion electrospray ionization (ESI) source. When the concentration of verubecestat ranged from 1 to 2500 ng/mL, the method exhibited good linearity. For verubecestat, the intra- and inter-day precision were determined with the values of 2.9–9.0% and 0.4–6.5%, respectively; and the accuracy ranged from −2.2% to 10.4%. Matrix effect, extraction recovery, and stability data were in line with the standard FDA guidelines for validating a bioanalytical method. The validity of the developed method was confirmed through the pharmacokinetic study.     

Comparative bioavailability of two zolpidem hemitartrate formulations in healthy human Brazilian volunteers using high-performance liquid chromatography coupled to tandem mass spectrometry

To assess the bioequivalence of two zolpidem hemitartrate formulations in 30 healthy volunteers. Plasma samples were obtained over a 24 h period. Plasma concentrations of zolpidem were analyzed by liquid chromatography coupled to tandem mass spectrometry with positive ion electrospray ionization using multiple reaction monitoring. Values of peak concentration (C_max), area under curve (AUC), half-life, elimination constant, volume of distribution and clearance showed statistically significant differences when comparing women (604.34 ng h/ml, 127.36 ng/ml, 4.4 h, 0.18 1/h, 50.56 L and 8.55 L/h, respectively) and men (276.1 ng h/ml, 70.9 ng/ml, 3.3 h, 0.26 1/h, 91.42 L and 24.34 L/h, respectively), receiving the same dose (5 mg), respectively. The geometric means with corresponding 90% confidence interval for Test/Reference percentage ratios were 99.73% (CI 93.69–106.16) for C_max, 97.44% (90% CI = 91.85–103.37%) for area under curve of plasma concentration until the last concentration observed (AUC_last) and 98.30% (90% CI = 92.48–104.49) for the area under curve between the first sample (pre-dosage) and infinity (AUC_0–inf). Since the 90% CI for AUC_last, AUC_0–inf and C_max ratios were within the 80–125% interval proposed by the US Food and Drug Administration, it was concluded that zolpidem hemitartrate formulation (5 mg orodispersible tablet) is bioequivalent to the zolpidem hemitartrate formulation (Patz SL 5 mg sublingual tablet) with regard to both the rate and the extent of absorption. A new formulation of zolpidem 2.5 mg may be useful in women for the same clinical benefits as the 5 mg formulation in men.     

LC–MS/MS analysis of puerarin and 18β-glycyrrhetinic acid in human plasma after oral administration of Samso-eum and its application to pharmacokinetic study

The aim of this study was to confirm pharmacokinetic screening of multiple components in healthy Korean subjects after oral administration of Samso-eum and perform quantitation of active components in the human plasma. Thirteen potential bioactive components [puerarin (PRR), daidzin, nodakenin, ginsenoside Rb1, 18β-glycyrrhetinic acid (18β-GTA), 6-shogaol, naringin, glycyrrhizin, hesperidin, platycodin D, naringenin, hesperetin, and 6-gingerol] were screened based on literature. The results showed that three analytes (daidzin, naringenin, and hesperetin) were detected in trace amounts. In addition, PRR and 18β-GTA were detected in human plasma after the oral administration of Samso-eum. In this study, a liquid chromatography–electrospray ionization-tandem mass spectrometry method was validated for the simultaneous determination of PRR and 18β-GTA in human plasma. This was the first study to evaluate pharmacokinetics of PRR and 18β-GTA after the usual oral dose of Samso-eum (30 g containing 102.48 mg PRR, 48.18 mg glycyrrhizin) in human subjects.