Rapid and Simultaneous Determination of Efavirenz, 8-Hydroxyefavirenz, and 8,14-Dihydroxyefavirenz Using LC�CMS�CMS in Human Plasma and Application to Pharmacokinetics in Healthy Volunteers

We developed a rapid and sensitive method for determining efavirenz, 8-hydroxyefavirenz, and 8,14-dihydroxyefavirenz in human plasma simultaneously using liquid chromatography?Ctandem mass spectrometry (LC?CMS?CMS). Three compounds and ritonavir, an internal standard, were extracted from plasma using ethyl acetate in the presence of 0.1 M sodium carbonate after incubation of ??-glucuronidase (500 U). After drying the organic layer, the residue was reconstituted in mobile phase (acetonitrile:20 mM ammonium acetate, 90:10, v/v) and injected onto a reversed-phase C₁₈ column. The isocratic mobile phase was eluted at 0.2 mL min^?1. The ion transitions monitored in multiple reaction-monitoring mode were m/z 314 ?? 244, 330 ?? 258, 346 ?? 262, and 721 ?? 296 for efavirenz, 8-hydroxyefavirenz, 8,14-dihydroxyefavirenz, and ritonavir, respectively. The retention time is 1.93, 1.70, 1.52, and 1.82 min for efavirenz, 8-hydroxyefavirenz, 8,14-dihydroxyefavirenz, and ritonavir, respectively. The coefficients of variation of the assay precision were less than 10.7%, and the accuracy was 90?C111%. The lower limits of quantification (LLOQ) were 5 ng mL^?1 for efavirenz and 8-hydroxyefavirenz. This method was used to measure the plasma concentrations of efavirenz and its metabolites from healthy volunteers after a single 600 mg oral dose of efavirenz. This analytical method is a very rapid, sensitive, and accurate to determine the pharmacokinetic profiles of efavirenz including its metabolites.     

Impact of environmentally friendly processing solvents on the properties of blade‐coated polymer solar cells

High‐performance polymer solar cells (PSCs) are typically fabricated by spin coating in inert atmosphere from toxic halogenated solvents such as 1,2‐dichlorobenzene (o‐DCB) and chlorobenzene. This fabrication process is potentially hazardous for both the humans and the environment and dramatically impacts the possibility for the organic photovoltaic technology to be adopted at large scale. In this work, efficient PSCs blade coated in air using nonhalogenated 1,2,4‐trimethylbenzene (TMB) as processing solvent are demonstrated. The active layer, based on a previously synthesized benchmark polymer PFQ2T‐benzodithiophene blended with [6,6]‐phenyl‐C61‐butyric acid methyl ester (PC₆₁BM), showed an enhanced solid‐state aggregation induced by the use of TMB. Compared to o‐DCB‐processed devices, the solar cells fabricated from TMB resulted 10% more efficient with a power conversion efficiency of 4.20%. Interestingly, the improved photovoltaic performance resulted from the combination of synergic effects promoted by a more favorable film morphology, such as high exciton dissociation efficiency and lower bimolecular recombinations resulting in higher charge collection efficiency at the electrodes. The positive effect of TMB, compared to that of commonly employed halogenated solvents, confirms the great potential of this approach for the development of efficient PSCs for practical applications with reduced environmental impact. © 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019 , 57, 487–494     

Imidazolium-Functionalized Chemically Robust Ionic Porous Organic Polymers (iPOPs) toward Toxic Oxo-Pollutants Capture from Water

Fabricating new and efficient materials aimed at containment of water contamination, in particular removing toxic heavy metal based oxo-anions (e. g. CrO₄²⁻, TcO₄⁻) holds paramount importance. In this work, we report two new highly stable imidazolium based ionic porous organic polymers (iPOPs) decorated with multiple interaction sites along with electrostatics driven adsorptive removal of such oxo-anions from water. Both the iPOPs (namely, iPOP-3 and iPOP-4) exhibited rapid sieving kinetics and very high saturation uptake capacity for CrO₄²⁻ anions (170 and 141 mg g⁻¹ for iPOP-3 and iPOP-4 respectively) and ReO₄⁻ (515.5 and 350.3 mg g⁻¹ for iPOP-3 and iPOP-4 respectively), where ReO₄⁻ anions being the non-radioactive surrogative counterpart of radioactive TcO₄⁻ ions. Noticeably, both iPOPs showed exceptional selectivity towards CrO₄²⁻ and ReO₄⁻ even in presence of several other concurrent anions such as Br⁻, Cl⁻, SO₄²⁻, NO₃⁻ etc. The theoretical binding energy calculations via DFT method further confirmed the preferential interaction sites as well as binding energies of both iPOPs towards CrO₄²⁻ and ReO₄⁻ over all other competing anions which corroborates with the experimental high capacity and selectivity of iPOPs toward such oxo-anions.     

Forced degradation studies of norepinephrine and epinephrine from dental anesthetics: Development of stability-indicating HPLC method and in silico toxicity evaluation

Injectable solutions containing epinephrine (EPI) and norepinephrine (NE) are not stable, and their degradation is favored mainly by the oxidation of catechol moiety. As studies of these drugs under forced degradation conditions are scarce, herein, we report the identification of their degradation products (DP) in anesthetic formulations by the development of stability-indicating HPLC method. Finally, the risk assessment of the major degradation products was evaluated using in silico toxicity approach. HPLC method was developed to obtain a higher selectivity allowing adequate elution for both drugs and their DPs. The optimized conditions were developed using a C18 HPLC column, sodium 1-octanesulfonate, and methanol (80:20, v/v) as mobile phase, with a flow rate of 1.5 mL/min, UV detection at 199 nm. The analysis of standard solutions with these modifications resulted in greater retention time for EPI and NE, which allow the separation of these drugs from their respective DPs. Then, five DPs were identified and analyzed by in silico studies. Most of the DPs showed important alerts as hepatotoxicity and mutagenicity. To the best of our acknowledgment, this is the first report of a stability-indicating HPLC method that can be used with formulations containing catecholamines.     

LC Method for Studies on the Stability of Sibutramine in Soft Gelatin Capsules

A sensitive and rapid liquid chromatographic method was successfully developed and validated for the determination of sibutramine hydrochloride in bulk and capsules. Sibutramine in the presence of its degradation products was analyzed using UV detection at 225 nm. Chromatography was performed on a reversed-phase C₈ (150 × 4.0 mm I.D., 5 μm) analytical column under isocratic conditions. The mobile phase was composed of acetonitrile:water (aqueous phase containing 0.3% triethylamine and pH adjusted to 7.0) (75:25, v/v) at a flow-rate of 1.1 mL min⁻¹. No chromatographic interference was found during the analysis. Light was the stress condition which most contributed to sibutramine degradation. The method showed a linear response (r > 0.999) from 30 to 90 μg mL⁻¹. The mean recovery for capsules was 101.2%. Inter-day assays showed relative standard deviations of 0.42 and 1.62% for bulk and capsules, respectively. The developed method is able to separate sibutramine from its major degradation products and it may be used in the quality control of this active pharmaceutical ingredient in both bulk and capsules.     

Silica-encapsulated CdTe/MPA quantum dots: microstructural,thermal, and chemical stability characterization

In this paper, we describe the synthesis of silica-encapsulated CdTe/MPA quantum dot (QD) nanocomposites (CdTe/MPA@SiO₂) at room temperature starting from water-soluble CdTe QDs capped with 3-mercaptopropionic acid (MPA) as surface ligand (CdTe/MPA), followed by their encapsulation with a thin layer of silica using the sol–gel process. The objective of this work was to evaluate the microstructural, thermal, and chemical properties of the encapsulated material as a way to evaluate these characteristics for possible applications in different technological areas. Transmission electron microscopy results proved that CdTe QDs (2.5 nm in size) were inside the SiO₂ nanoparticles, and the spherical CdTe/MPA@SiO₂ nanocomposite with a 69-nm thick shell. The photoluminescence intensity was evaluated as a function of pH in the range of 2–12. The CdTe/MPA@SiO₂ nanocomposite showed better chemical stability and greater intensity of photoluminescence in the pH 2–12 range than CdTe/MPA. In addition, the CdTe/MPA@SiO₂ nanocomposites showed good heat stability up to 125 °C. The changes in their optical properties were also evaluated by means of photoluminescence spectroscopy. The materials were also characterized by diffuse reflectance spectroscopy, X-ray diffraction, infrared spectroscopy, and thermogravimetric analysis.

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The hydrolysis of the saponins ofAralia manchurica

Summary 1. To perform the hydrolysis of the technical preparation Saparal the optimum conditions are 30-min heating in a 1:1 mixture of acetic acid and 20% sulfuric acid or a 1:1 mixture of acetic acid and 30% sulfuric acid.2. It has been established that the hydrolysis of Saparal is a first-order reaction with K_h = 0.1855.Pyatigorsk Pharmaceutical Institute. Translated from Khimiya Prirodnykh Soedinenii, No. 5, pp. 590–592, September–October, 1978.     

2,2′-Bipyridine-6,6′-bis(carbothioamide) metal complexes

Complexes of 2,2-bipyridine-6,6-bis(carbothioamide), obtained with a variety of metal cations, were characterised by microanalyses, molar conductivities and by i.r. and n.m.r. (for diamagnetic compounds) spectra. The iron(II) complex was also characterised by Mössbauer spectroscopy. The spectral data indicate that, in all cases, the ligand coordinates to the metal through one pyridine nitrogen and one sulphur.