Determination of metoprolol enantiomers in human urine by GC-MS using (−)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride as a chiral derivatizing agent

Summary A method for the assay of R-(+)- and S-(−)- metoprolol in human urine has been developed using gas chromatography-mass spectrometry. The method involved purification by liquid-liquid extraction and derivatization with N-methyl-N-(trimethylsilyl)trifluoroacetamide to form an O-silyl ether, followed by subsequent chiral derivatization with (−)-α-methoxy-α-(trifluoromethyl)phenylacetyl chloride to form diastereomeric amide. The reaction was rapid and the diastereomeric derivatives were well resolved. Quantitation was performed by selected-ion monitoring of fragment ions of the diastereomers in electron impact ionization mode. No racemization was found during the reaction. The detection limit was 0.5 ng·mL⁻¹. The intra-day variation ranged between 0.38 and 7.86% in relation to the measured concentration and inter-day variation was 2.26–8.06%. The method has been applied to the determination of R-(+)-and S-(−)- metoprolol in human urine from healthy volunteers dosed with racemic metoprolol tartrate.     

Orientation control of perovskite thin films on glass substrates by the application of a seed layer prepared from oxide nanosheets

Orientation control of perovskite compounds was investigated by the application of a seed layer prepared from oxide nanosheets. An aqueous suspension of oxide nanosheets was prepared by the exfoliation of a layered compound of KCa₂Nb₃O₁₀ oxide grains. A seed layer composed of (TBA)Ca₂Nb₃O₁₀ nanosheets (TBA = tetrabutylammonium) was formed on a glass substrate by simply dip coating it in the suspension. Two kinds of perovskite compounds, LaNiO₃ (LNO) and Pb(Zr,Ti)O₃ (PZT) with a preferred orientation of (00l) were successfully grown on this seeded glass substrate. In this study, the relation between lattice mismatch and electrical properties is investigated. A large, oriented PZT film with a size of 5 ×4 cm shows an improved P-E hysteresis behavior by use of this orientation control.     

Simultaneous assignment of all diastereotopic protons in strychnine using RDCs: PELG as alignment medium for organic molecules

The concept of using residual dipolar couplings (RDCs) for the structure determination of organic molecules is applied to the simultaneous assignment of all diastereotopic protons in strychnine. To use this important NMR parameter the molecule has to be aligned in the magnetic field. Here we present a new alignment medium for organic substrates. The optimization of the alignment properties of mixtures of poly-gamma-ethyl-L-glutamate (PELG) and CDCl(3) are described and the alignment properties of PELG at different concentrations are evaluated. A comparison of PELG with poly-gamma-benzyl-L-glutamate (PBLG) shows considerable differences in the magnitude of alignment for strychnine in the two alignment media. PELG induces a lower degree of order and makes the measurement of residual dipolar couplings (RDCs) in strychnine possible. All one-bond C-H RDCs of strychnine in PELG were determined by using 2D heteronuclear single quantum coherence (HSQC) spectroscopy. The strategy for the extraction of RDCs for methylene groups is described in detail. The RDCs and order parameters are used to assign pairs of diastereotopic protons. This methodology can distinguish not only one pair of diastereotopic protons but it can be used to assign all pairs of diastereotopic protons simultaneously. Two different calculation approaches to achieve this task are described in detail.