Migration behaviour and separation of tramadol metabolites and diastereomeric separation of tramadol glucuronides by capillary electrophoresis

Capillary electrophoresis with UV detection was used to separate tramadol (TR), a centrally acting analgesic, and its five phase I (M1, M2, M3, M4, M5) and three phase II metabolites (glucuronides of M1, M4 and M5). Several factors were evaluated in optimisation of the separation: pH and composition of the background electrolyte and the influence of a micellar modifier, sodium dodecyl sulfate. Baseline separation of TR and all the analytes was obtained with use of 65 mM tetraborate electrolyte solution at pH 10.65. The lowest concentrations of the analytes that could be detected were below 1 microM for the O-methylated, below 2 microM for the phenolic and ca. 7 microM for the glucuronide metabolites. The suitability of the method for screening of real samples was tested with an authentic urine sample collected after a single oral dose (50 mg) of TR. After purification and five-fold concentration of the sample (solid-phase extraction with Oasis MCX cartridges), the parent drug TR and its metabolites M1, M1G, M5 and M5G were easily detected, in comparison with standards, in an interference-free area of the electropherogram. Diastereomeric separation of TR glucuronides in in vitro samples was achieved with 10 mM ammonium acetate-100 mM formic acid electrolyte solution at pH 2.75 and with basic micellar 25 mM tetraborate-70 mM SDS electrolyte solution at pH 10.45. Both separations showed that glucuronidation in vitro produces glucuronide diastereomers in different amounts. The authentic TR urine sample was also analysed by micellar method, but unambiguous identification of the glucuronide diastereomers was not achieved owing to many interferences.     

On the two isomeric tris(perchlorothienyl)methyl radicals

The two isomeric tris(trichlorothienyl)carbinols have been synthesized. Upon treatment with acid the tris(trichlorothienyl)carbenium ions were formed, which upon reduction with iodide gave the tris(trichlorothienyl)methyl radicals, which were studied by epr-spectroscopy. The β-isomer, the tris(2,4,5-trichloro-3-thienyl)methyl radical, was much more stable than the α-isomer and showed great similarity to the perchlorotrityl radical.     

High-performance thin-layer chromatography method for assessment of the quality of combinatorial libraries,and comparison with liquid chromatography-ultraviolet-mass spectrometry

A high-performance thin-layer chromatography (HPTLC) method was developed for fast evaluation of the purity of solid-phase synthesis products. The results obtained were in good agreement with results obtained by the LC-MS method (r(2) = 0.8404) or by the LC-UV method (r(2) = 0.8053), confirming the suitability of HPTLC for purity analysis of combinatorial syntheses. The synthesis products can be quantified and identified by measuring UV densitograms or in situ UV spectra or by ESI-MS after isolation of the zone of interest. A new, simple, and fast method for transferring the zone of the analyte from the plate to the ESI-MS equipment is described. The new HPTLC method enables rapid and efficient analysis of approximately 40 samples in parallel. As such, it offers a cheaper and easier way to analyze the purity of synthesis products than the commonly used LC-UV-MS.     

Synthesis of 5-cyclopropyluracil and 5-cyclopropylcytosine by the Pd(0)-catalyzed coupling reaction

5-Cyclopropyluracil and cyclopropylcytosine were prepared by the Pd(0)-catalyzed coupling reaction of 5-bromo-2,4-di(trimethylsilyloxy)pyrimidine and 5-bromo-2,4-O,N-bis-trimethylsilylcytosine with tributylstan-nylcyclopropane. The reactions also gave dehalogenated pyrimidine bases as by-products. Attempts to use 2,4-O,N-bis-trimethylsilyl-5-iodocytosine as the halide gave complete dehalogenation.     

Thermal and spectroscopic investigation of europium and samarium sulphates hydrates by TG-FTIR and ICP-MS techniques

The investigation of europium(III) sulphate hydrate and samarium(III) sulphate hydrate was performed by thermal analysis (TG-DTG) and simultaneous infrared evolved gas analysis-Fourier transformed infrared (EGA-FTIR) spectroscopy. The TG, DTG and DTA curves were recorded at the 25–1400 °C in the dynamic air atmosphere by TG/DTA analyser. The infrared evolved gas analysis was obtained on the FTIR spectrometer. Eu₂(SO₄)₃·nH₂O (n = 3.97) and Sm₂(SO₄)₃·nH₂O (n = 8.11) were analysed, the dehydration and decomposition steps were investigated and the water content was calculated. The formation of different oxysulphates was studied.

The trace rare earth elements in Eu and Sm sulphates were determined by ICP-MS. The concentration of trace Eu, Sm, La, Gd, Y and Ce ranged from 3.9 × 10⁻⁶ to 1.5 × 10⁻⁴% (m/m).     

Novel Thiazole-Containing Complexing Agents and Luminescence of Their Europum(III) and Terbium(III) Chelates

The synthesis of novel thiazole-containing complexing agents and their luminescence properties with Eu^III and Tb^III ions are reported. One of these terpyridine analogues was also tested as an Eu^III labelling reagent, and its luminescence properties as an antibody conjugate were studied.     

Inverse problems with partial data for a Dirac system: A Carleman estimate approach

We prove that the material parameters in a Dirac system with magnetic and electric potentials are uniquely determined by measurements made on a possibly small subset of the boundary. The proof is based on a combination of Carleman estimates for first and second order systems, and involves a reduction of the boundary measurements to the second order case. For this reduction a certain amount of decoupling is required. To effectively make use of the decoupling, the Carleman estimates are established for coefficients which may become singular in the asymptotic limit.     

Quasiregular maps on Carnot groups

In this paper we initiate the study of quasiregular maps in a sub-Riemannian geometry of general Carnot groups. We suggest an analytic definition for quasiregularity and then show that nonconstant quasiregular maps are open and discrete maps on Carnot groups which are two-step nilpotent and of Heisenberg type; we further establish, under the same assumption, that the branch set of a nonconstant quasiregular map has Haar measure zero and, consequently, that quasiregular maps are almost everywhere differentiable in the sense of Pansu. Our method is that of nonlinear potential theory. We have aimed at an exposition accessible to readers of varied background. Dedicated to Seppo Rickman on his sixtieth birthday J.H. was partially supported by NSF, the Academy of Finland, and the A. P. Sloan Foundation. I.H. was partially supported by the EU HCM contract no. CHRX-CT92-0071.     

Solvability of Minimal Graph Equation Under Pointwise Pinching Condition for Sectional Curvatures

We study the asymptotic Dirichlet problem for the minimal graph equation on a Cartan–Hadamard manifold M whose radial sectional curvatures outside a compact set satisfy an upper bound

$$\begin{aligned} K(P)\le - \frac{\phi (\phi -1)}{r(x)^2} \end{aligned}$$

and a pointwise pinching condition

$$\begin{aligned} |K(P) |\le C_K|K(P') | \end{aligned}$$

for some constants \(\phi >1\) and \(C_K\ge 1\), where P and \(P'\) are any 2-dimensional subspaces of \(T_xM\) containing the (radial) vector \(\nabla r(x)\) and \(r(x)=d(o,x)\) is the distance to a fixed point \(o\in M\). We solve the asymptotic Dirichlet problem with any continuous boundary data for dimensions \(n=\dim M>4/\phi +1\).