A Simple Strategy to Improve the Accuracy of the Injection Step in Batch Injection Analysis Systems with Amperometric Detection

In this study, we describe for the first time the application of an internal standard method to compensate for random errors associated with the injection procedure in batch injection analysis (BIA) systems with multiple pulse amperometric detection. A sequence of potential pulses was selected in such a way that the internal standard (IS) compound was detected individually at one potential pulse and both the IS and analyte, were detected at another potential pulse. The current ratio (I_IS+analyte/I_IS) was used in the construction of the calibration curve and then to compensate for random errors. The use of disposable syringes or manual pipettes in BIA systems increases the robustness of the method and dispenses with skilled operators.     

Local–global multiscale model reduction for flows in high-contrast heterogeneous media

In this paper, we study model reduction for multiscale problems in heterogeneous high-contrast media. Our objective is to combine local model reduction techniques that are based on recently introduced spectral multiscale finite element methods (see [19]) with global model reduction methods such as balanced truncation approaches implemented on a coarse grid. Local multiscale methods considered in this paper use special eigenvalue problems in a local domain to systematically identify important features of the solution. In particular, our local approaches are capable of homogenizing localized features and representing them with one basis function per coarse node that are used in constructing a weight function for the local eigenvalue problem. Global model reduction based on balanced truncation methods is used to identify important global coarse-scale modes. This provides a substantial CPU savings as Lyapunov equations are solved for the coarse system. Typical local multiscale methods are designed to find an approximation of the solution for any given coarse-level inputs. In many practical applications, a goal is to find a reduced basis when the input space belongs to a smaller dimensional subspace of coarse-level inputs. The proposed approaches provide efficient model reduction tools in this direction. Our numerical results show that, only with a careful choice of the number of degrees of freedom for local multiscale spaces and global modes, one can achieve a balanced and optimal result.     

Experimental NMR and MS study of benzoylguanidines. Investigation of E/Z isomerism

Molecules containing the guanidinic nuclei possess several pharmacological applications, and knowing the preferred isomers of a potential drug is important to understand the way it operates pharmacologically. Benzoylguanidines were synthesized in satisfactory to good yields and characterized by NMR, Electrospray Ionization Mass Spectrometry (ESI‐MS) and Fourrier Transform InfraRed Spectroscopy techniques (FTIR). E/Z isomerism of the guanidines was studied and confirmed by NMR analysis in solution (¹H‐¹³C Heteronuclear Single Quantum Coherence (HSQC) and Heteronuclear Multiple‐Bond Correlation (HMBC), ¹H‐¹⁵N HMBC, ¹H‐¹H Correlation Spectroscopy (COSY) and Nuclear Overhauser Effect Spectroscopy (NOESY) experiments) at low temperatures. Compounds with p‐Cl and p‐Br aniline moiety exist mainly as Z isomer with a small proportion of E isomer, whereas compounds with p‐NO2 moiety showed a decrease in proportion of isomer Z. The results are important for the application of these molecules as enzymatic inhibitors. Copyright © 2013 John Wiley & Sons, Ltd.     

Quantum histories without contrary inferences

In the consistent histories formulation of quantum theory it was shown that it is possible to retrodict contrary properties. We show that this problem do not appear in our formalism of generalized contexts for quantum histories.     

Rapid and sensitive ultra‐high‐pressure liquid chromatography method for quantification of antichagasic benznidazole in plasma: application in a preclinical pharmacokinetic study

Benznidazole (BNZ) and nifurtimox are the only drugs available for treating Chagas disease. In this work, we validated a bioanalytical method for the quantification of BNZ in plasma aimed at improving sensitivity and time of analysis compared with the assays already published. Furthermore, we demonstrated the application of the method in a preclinical pharmacokinetic study after administration of a single oral dose of BNZ in Wistar rats. A Waters® Acquity UHPLC system equipped with a UV–vis detector was employed. The method was established using an Acquity® UHPLC HSS SB C₁₈ protected by an Acquity® UHPLC HSS SB C₁₈ VanGuard guard column and detection at 324 nm_. The mobile phase consisted of ultrapure water–acetonitrile (65:35), and elution was isocratic. The mobile phase flow rate was 0.55 mL/min, the volume of injection was 1 μL, and the run time was just 2 min. The samples were kept at 25°C until injection and the column at 45°C for the chromatographic separation. The sample preparation was performed by a rapid protein precipitation with acetonitrile. The linear concentration range was 0.15–20 µg/mL. The pharmacokinetic parameters of BNZ in rats were determined and the method was considered sensitive, fast and suitable for application in pharmacokinetic studies. Copyright © 2014 John Wiley & Sons, Ltd.     

Determination of mazindol in human oral fluid by high performance liquid chromatography–electrospray ionization mass spectrometry

Brazil is one of the countries most affected by abuse of stimulant medications by professional drivers, especially fenproporex, amfepramone and mazindol. Even though their sale is banned, they can be found in illegal markets, such as those located on the country's borders. The use of oral fluid to monitor drug levels has many advantages over plasma and urine because it is noninvasive, easier to collect and more difficult to adulterate. The aim of this study was to develop and validate a sensitive and specific method to quantify mazindol in human oral fluid by liquid chromatography–mass spectrometry (LC‐MS). The LC system consisted of an LC‐MS system operated in selected ion monitoring mode. The mobile phase was composed of water at pH 4.0, acetonitrile and methanol (60:15:25 v/v/v) at a flow rate of 1.0 mL/min and propranolol was used as internal standard. Total running time was 10 min. The lower limit of quantification was 0.2 ng/mL and the method exhibited good linearity within the 0.2–20 ng/mL range (r = 0.9987). A rapid, specific, sensitive, linear, precise and accurate method was developed for determination of mazindol in human oral fluid according to European Medicines Agency guidelines, and is suitable for monitoring mazindol levels in oral fluid of professional drivers. Copyright © 2014 John Wiley & Sons, Ltd.