Determination of volatile residual solvents in pharmaceutical products by headspace liquid-phase microextraction gas chromatography-flame ionization detector

This paper demonstrates headspace liquid-phase microextraction (HS-LPME) as used for the determination of volatile residual solvents in pharmaceutical products. This method is based on headspace liquid-phase microextraction capillary column gas chromatography. Under optimum conditions, the linerary of the method ranged from 1 to 1,000 mg l⁻¹. The limits of detection are 0.2–2.0 mg l⁻¹ and relative standard deviations (RSD) for most of the volatile solvents were below 10%. This novel method is applied to the analysis of volatile residual solvents in pharmaceutical products with satisfactory results.     

Isotopengeochemisches Kompartimentmodell des Stickstoffkreislaufs

Es wird ein Modell des globalen Kreislaufs des Stickstoffs und seiner Isotope beschrieben, das die folgenden geochemischen Reservoire berücksichtigt: Stickstoff in Magmatiten, Stickstoff in Metamorphiten, Stickstoff in Sedimentiten und Stickstoff der Atmosphäre. Das Modell berücksichtigt den Stickstoffaustausch zwischen Magmatiten und dem Oberen Mantel, den Übergang des Stickstoffs aus Magmatiten und Metamorphiten in die Atmosphäre und den Stickstoffaustausch zwischen Sedimentiten und der Atmosphäre und andere geochemische Prozesse.

Auf der Grundlage aller gegenwärtig zugänglichen δ¹⁵N-Werte magmatischer, metamorpher und sedimentärer Gesteine und plausibler Annahmen über die Isotopieeffekte, die bei der Bildung dieser Stickstoffflüsse wirken, werden – unter Benutzung des mathematischen Formalismus der Kompartimenttheorie – quantitative Aussagen abgeleitet über das Ausmaß des Stickstoffaustausches zwischen der Erdkruste und dem Oberen Mantel und über andere Stickstoffflüsse, die den globalen Stickstoffkreislauf charakterisieren.     

A modified approach to team-based learning in linear algebra courses

This paper documents the author’s adaptation of team-based learning (TBL), an active learning pedagogy developed by Larry Michaelsen and others, in the linear algebra classroom. The paper discusses the standard components of TBL and the necessary changes to those components for the needs of the course in question. There is also an empirically controlled analysis of the effects of TBL on the student learning experience in the first year of TBL use.     

Optimization of Verapamil Drug Analysis by Excitation-Emission Fluorescence in Combination with Second-order Multivariate Calibration

Excitation emission fluorescence matrices (EEMs) of Verapamil drug were obtained by direct and by derivatization fluorescence spectroscopy. The fluorescence excitation and emission wavelengths were displaced to longer wavelengths and the fluorescence intensity was enhanced upon derivation with respect to the native fluorescence of the drug. The complete EEM of the native fluorescence of the drug and of the derivatization product were rapidly acquired by using a charged-coupled device detector (CCD), which is advantageous in terms of speed in the analysis, with respect to the use of a conventional photomultiplier detector. The EEMs were analyzed by several second-order multivariate calibration methods exploiting the second order advantage. The three-dimensional decomposition methods used, based in different assumptions about the trilinearity of the three way data structure under analysis, were parallel factor analysis (PARAFAC), bilinear least squares (BLLS), parallel factor analysis 2 (PARAFAC2) and multivariate curve resolution—alternating least squares (MCR-ALS). The determination was performed by using the standard addition approach. The figures of merit of the PARAFAC and BLLS methods were calculated, obtaining a lower limit of detection with the derivatization procedure, when compared with the direct measurement of the fluorescence of the drug. In Verapamil drug the best estimations were found with the BLLS and the MCR-ALS models. In the quantification of Verapamil in a pharmaceutical formulation the best estimation, when compared with the result obtained by the US Pharmacopeia high performance liquid chromatography approach, was obtained by direct fluorescence spectroscopy with MCR-ALS and by derivatization fluorescence spectroscopy with the PARAFAC2 model.     

A Facile Strategy for Construction of Sensor for Detection of Ondansetron and Investigation of its Redox Behavior and Thermodynamic Parameters

A sodium dodecylsulfate‐doped polypyrrole (SDS‐PPy) film was elaborated on glassy carbon electrode (GCE) by an electrodeposition method in phosphate buffer solution (pH 2.0) containing pyrrole (Py) and sodium dodecyl sulfate (SDS). SDS‐PPy/GCE was used for the construction of sensor, which showed excellent electrochemical response for the detection of ondansetron (OND) compared to conventional PPy. The application of the square wave (SW), with the adsorptive accumulation, indicates a maximum response at 1.33 V in H₂SO₄ (0.5 M). The influence of experimental parameters on determination of OND is discussed. The adsorptive stripping technique showed to be more sensitive, giving responses twice as big as those of non‐accumulated OND. The substantial improvement of response permits the development of an electroanalytical technique with a linear concentration in the range (1.0–80 μM), low detection (0.09 μM), and quantification limits (0.3 μM), and acceptable relative standard deviations of repeatability (0.59 %), and reproducibility (1.51 %). Consequently, this electrode is promising candidate for an accurate electroanalytical determination of OND in pharmaceutical samples with high sensitivity and selectivity, good accuracy and precision. The electrooxidation of OND at SDS‐PPy/GCE at various temperatures were studied by cyclic voltammetry to evaluate both the kinetic (k_s and E_a) and thermodynamic (ΔG*, ΔH* and ΔS*) parameters.     

New Opportunities for the Utilization of the Sulfoximine Group in Medicinal Chemistry from the Drug Designer's Perspective**

Extension of the medicinal chemistry toolbox is in the vital interest of drug designers. However, the diffusion of an innovation can be a lengthy process. Along these lines, it took almost 70 years before the use of the sulfoximine group reached a critical mass in medicinal chemistry. Even though interest in this versatile functional group has increased exponentially in recent years, there is ample room for further innovative applications. This Review highlights emerging trends and opportunities for drug designers for the utilization of the sulfoximine group in medicinal chemistry, such as in the construction of complex molecules, proteolysis targeting chimeras (PROTACs), antibody-drug conjugates (ADCs) and novel warheads for covalent inhibition.     

An Electrochemical Sensor Based on Silver Nanoparticles‐Benzalkonium Chloride for the Voltammetric Determination of Antiviral Drug Tenofovir

A simple voltammetric nanosensor was described for the highly sensitive determination of antiviral drug Tenofovir. The benzalkonium chloride and silver nanoparticles were associated to build a nanosensor on glassy carbon electrode. Surface characterictics were achieved using scanning electron microscopic technique. The voltammetric measurements were performed in pH range between 1.0 and 10.0 using cyclic, adsorptive stripping differential pulse and adsorptive stripping square wave voltammetry. The linear dependence of the peak current on the square root of scan rates and the slope value (0.770) demonstrated that the oxidation of tenofovir is a mix diffusion‐adsorption controlled process in pH 5.70 acetate buffer. The linearity range was found to be 6.0×10⁻⁸–1.0×10⁻⁶ M, and nanosensor displayed an excellent detection limit of 2.39×10⁻⁹ M by square wave adsorptive stripping voltammetry. The developed nanosensor was successfully applied for the determination of Tenofovir in pharmaceutical dosage form. Moreover, the voltammetric oxidation pathway of tenofovir was also investigated at bare glassy carbon electrode comparing with some possible model compounds (Adenine and Adefovir).     

Selective Determination of Verapamil in Pharmaceutics and Urine Using a Boron‐doped Diamond Electrode Coupled to Flow Injection Analysis with Multiple‐pulse Amperometric Detection

This work presents a simple and low‐cost method for fast and selective determination of Verapamil (VP) in tablets and human urine samples using a boron‐doped diamond working electrode (BDD) coupled to a flow injection analysis system with multiple pulse amperometric detection (FIA‐MPA). The electrochemical behaviour of VP in 0.1 mol L⁻¹ sulfuric acid showed three merged oxidation peaks at around +1.4 V and upon reverse scan, one reduction peak at 0.0 V (vs. Ag/AgCl). The MPA detection was performed applying a sequence of three potential pulses on BDD electrode: (1) at +1.6 V for VP oxidation, (2) at +0.2 V for reduction of the oxidized product and (3) at +0.1 V for cleaning of the working electrode surface. The FIA system was optimized with injection volume of 150 μL and flow rate of 3.5 mL min⁻¹. The method showed a linear range from 0.8 to 40.0 μmol L⁻¹ (R>0.99) with a low limit of detection of 0.16 μmol L⁻¹, good repeatability (RSD<2.2 %; n=10) and sample throughput (45 h⁻¹). Selective determination of VP in urine was performed at+0.2 V due to absence of interference from ascorbic and uric acids in this potential. The addition‐recovery tests in both samples were close to 100 % and the results were similar to an official method.     

Organocatalytic stereoselective conjugate addition of 3-substituted oxindoles with in situ generated ortho-quinone methides

A novel method for the stereoselective conjugate addition of 3-substituted oxindoles to in situ generated o-QMs was described. This process was catalyzed efficiently by a cinchonidine-derived squaramide catalyst in oil-water phase, furnishing the corresponding 3,3-disubsituted oxindole derivatives in moderate to high yields (up to 98%) with high stereoselectivities (up to 95%?ee, 15.4:1?dr). The utility of this reaction was also investigated by the gram-scale synthesis and derivatization of one of the products.     

Ferric nitrate-promoted oxidative esterification of toluene with N-hydroxyphthalimide: Synthesis of N-hydroxyimide esters

A ferric nitrate-promoted cross-dehydrogenative coupling reaction of N-hydroxyphthalimide (NHPI) with toluene derivatives is reported. The reaction proceeded smoothly using molecular oxygen as an oxidant, providing an efficient method for the synthesis of N-hydroxyimide esters. Furthermore, a plausible mechanism was proposed.