Matrix effect screening for cloud-point extraction combined with liquid chromatography coupled to mass spectrometry: Bioanalysis of pharmaceuticals.

Matrix effects are one of the most challenging issues in the analysis of complex samples using liquid chromatography coupled to mass spectrometry (LC-MS). Apart from the instrumental origin, these effects are also related to sample preparation. Cloud-point extraction (CPE) is rarely combined with LC-MS as it requires the use of surfactants which might interfere with droplet evaporation. Thus, they are suspected to cause a significant matrix effect (signal suppression). In this paper, 73 model drugs with different physicochemical properties were screened to analyse how susceptible LC-MS is to the absolute and relative matrix effect (ME) when coupled with CPE for measurements in human plasma. Three combinations of the surfactant Triton X-114 concentration (1.5% or 6%) and extraction temperature (40 or 55 °C) in six pH values gave over 1300 analyte-sample preparation condition pairs. A new term - surfactant effect (calculated for the standard solution) - allowed us to distinguish between the surfactant effect and that related to interferences from human plasma. The screening revealed that CPE combined with LC-MS is not related to a significant ME in the optimal pH of extraction. A significant absolute ME (<85% or>115%) was observed only for 25% of the analytes. Data processing (principal component analysis, classification trees, partial least squares-discriminant analysis) based on the extraction conditions and molecular descriptors helped to identify compounds prone to the matrix effect and speed up method development. A low surfactant concentration and low temperature decreased both the absolute and relative ME. pH of the extraction influenced only the relative ME. Low retention time reduced the risk of relative ME, whereas high polarity and the possibility of hydrogen bond formation minimized the occurrence of the surfactant effect and absolute ME. A significant relative ME (>15%) was observed only for 11% of the compounds, thus CPE merged with LC-MS allowed to measure drug concentrations in a reliable manner for majority of compounds. The presented approach may be further applied to other analytes and matrices.

How does the NMR thermometer work? Application of combined quantum molecular dynamics and GIPAW calculations into the study of lead nitrate.

Lead nitrate is an inorganic salt, commonly used for the accurate temperature determination in the solid state NMR spectroscopy, due to the strong temperature dependence of the 207 Pb chemical shift. As the reason for this phenomenon remained unknown, the main purpose of this study was to explain this temperature dependence at the molecular level. To achieve this, combined CASTEP geometry optimization, quantum molecular dynamics at chosen temperatures and GIPAW NMR computations were performed. Due to the previous literature reports on inaccuracy in the calculation of 207 Pb NMR parameters using GIPAW, a large emphasis was put on the optimization of computational method. The application of quantum molecular dynamics provided the simulation of the temperature-dependent vibrational motions and enabled to accurately compute the changes in the value of Pb δiso resulting from them. © 2018 Wiley Periodicals, Inc.

Selenized polysaccharides - Biosynthesis and structural analysis.

The main objective of our research was to analyze the structure of the Se-containing polysaccharides and to examine how the selenium is bound to the polysaccharide molecule. During investigation of the biosynthesis of new immunomodulators, we isolated a selenium (Se)-containing polysaccharide-protein fraction containing proteoglycans of molecular weights of 3.9 × 106 Da and 2.6 × 105 Da, composed of glucose or mannose, nearly 8% of protein and 190 µg Se/g dry weight. X-ray absorption spectroscopy (XAS) data analysis in the near edge region (XANES) confirmed that selenium in the Se-polysaccharides structure is present at the -II oxidation state and that Se is organically bound. The simulation analysis in the EXAFS (extended X-ray absorption fine structure) region suggested that selenium is most likely bound by a glycosidic-link in a ß-1,3 or α-1,4-glycosidic bond or substituted for oxygen in a pyranosidic ring. Calculations performed with Gaussian 03 software predicted deformations in the polysaccharide structure caused by the incorporation of the selenium atom including change in bond lengths and torsion angles and, as a result, disappearance of hydrogen bonds in the vicinity of the selenium atoms.