A sensitive and specific precursor ion scanning approach in liquid chromatography/electrospray ionization tandem mass spectrometry to detect methylprednisolone acetate and its metabolites in rat urine

A new, simple, sensitive and specific liquid chromatography/electrospray ionization tandem mass spectrometric (LC/ESI‐MS/MS) method in precursor ion scanning (PIS) mode has been developed for the rapid detection of methylprednisolone acetate (MPA) and its metabolites in rat urine. A suitable product ion specific for methylprednisolone (MP) and MPA was selected after a fragmentation study on 20 (cortico)steroids at different collision energies (5–40 eV). Urine samples were simply treated with acetonitrile then dried in a SpeedVac system. The method was validated and compared with other PIS methods for detecting corticosteroids in human urine. It was more sensitive, with limit of detection (LOD) and lower limit of quantitation (LLOQ), respectively, of 5 and 10 ng mL^?1. The method was applied for the analysis of rat urine collected before and after (24, 48, 72 h) intra‐articular (IA) injection of a marketed formulation of MPA (Depo‐Medrol®). MS/MS acquisitions were taken at different collision energies for the precursor ions of interest, detected in PIS mode, to verify the MP‐related structure. Six different metabolites were detected in rat urine, and their chemical structures were assigned with a computational study. Copyright © 2010 John Wiley & Sons, Ltd.     

Composition of Lie transforms with rigorous estimates and applications to Hamiltonian perturbation theory

In this paper we exhibit a rigorous perturbation theory for nearly integrable Hamiltonian systems, based on the composition of Lie Transforms. Precisely, we first study the algorithm for the composition of Lie transforms, and provide rigorous estimates for the convergence radius and the truncation errors of the series; then we use our estimates for a particular model-example, namely a system of weakly coupled harmonic oscillators having Diophantine frequencies, and work out Nekhoroshev-like exponential estimates for the stability times.     

Metal complexes of C2-symmetric chiral bipyridine ligands. X-ray structure of [bis(nitrato)(4S,5S)-2,2-dimethyl-4,5-bis(2-pyridyl)-1,3-dioxolane cobalt(II)]

Chelating properties of C₂-symmetric chiral bipyridine ligands are discussed. In particular we report the syntheses of the cobalt(II), nickel(II), zinc(II) and copper(II) complexes of (4S,5S)-2,2-dimethyl-4,5-bis(2-pyridyl)-1,3-dioxolane. All compounds have been characterized by IR spectroscopy, and an X-ray diffraction analysis has been carried out on one of them: Co(L)(NO₃)₂. The ligand coordinates the cobalt atom by the two nitrogen donors N(1) and N(2). A seven-membered chelation ring is formed, presenting a remarkable non-crystallographic twofold pseudosymmetry around the axis connecting Co and the midpoint of the C(6)–C(7) bond. The metal also binds two monodentate nitrates, thus completing a distorted coordination tetrahedron.     

Riesz transforms for a non-symmetric Ornstein-Uhlenbeck semigroup

Let (ℋ _t ) _t≥0 be the Ornstein-Uhlenbeck semigroup on ℝ ^d with covariance matrix I and drift matrix −λ(I+R), where λ>0 and R is a skew-adjoint matrix and denote by γ _∞ the invariant measure for (ℋ _t ) _t≥0. Semigroups of this form are the basic building blocks of Ornstein-Uhlenbeck semigroups which are normal on L ²(γ _∞). We investigate the weak type 1 estimate of the Riesz transforms for (ℋ _t ) _t≥0. We prove that if the matrix R generates a one-parameter group of periodic rotations then the first order Riesz transforms are of weak type 1 with respect to the invariant measure γ _∞. We also prove that the Riesz transforms of any order associated to a general Ornstein-Uhlenbeck semigroup are bounded on L ^p (γ _∞) if 1<p<∞. The authors have received support by the Italian MIUR-PRIN 2005 project “Harmonic Analysis” and by the EU IHP 2002-2006 project “HARP”.     

A New Indirect Electroanalytical Method to Monitor the Contamination of Natural Waters with 4‐Nitrophenol Using Multiwall Carbon Nanotubes

The electrochemical detection of the hazardous pollutant 4‐nitrophenol (4‐NP) at low potentials, in order to avoid matrix interferences, is an important research challenge. This study describes the development, electrochemical characterization and utilization of a multiwall carbon nanotube (MWCNT) film electrode for the quantitative determination of 4‐NP in natural water. Electrochemical impedance spectroscopy measurements showed that the modified surface exhibits a decrease of ca. 13 times in the charge transfer resistance when compared with a bare glassy carbon (GC) surface. Voltammetric experiments showed the possibility to oxidize a hydroxylamine layer (produced by the electrochemical reduction of 4‐NP on the GC/MWNCT surface) in a potential region which is approximately 700 mV less positive than that needed to oxidize 4‐NP, thus minimizing the interference of matrix components. The limit of detection for 4‐NP obtained using square‐wave voltammetry (0.12 μmol L^?1) was lower than the value advised by EPA. A natural water sample from a dam located in São Carlos (Brazil) was spiked with 4‐NP and analyzed by the standard addition method using the GC/MWCNT electrode, without any further purification step. The recovery procedure yielded a value of 96.5% for such sample, thus confirming the suitability of the developed method to determine 4‐NP in natural water samples. The electrochemical determination was compared with that obtained by HPLC with UV‐vis detection.     

N-propargylic beta-enaminones: common intermediates for the synthesis of polysubstituted pyrroles and pyridines.

N-Propargylic beta-enaminones have been used as common intermediates for the synthesis of polysubstituted pyrroles and pyridines. Best results have been obtained using DMSO as solvent. In the presence of Cs(2)CO(3) N-propargylic beta-enaminones are cyclized to pyrroles in good to high yields, whereas omitting bases and using CuBr leads to the selective formation of pyridines.     

ATRP synthesis and association properties of thermoresponsive anionic block copolymers

Thermosensitive anionic block copolymers of sodium 2‐acrylamido‐2‐methylpropanesulfonate (AMPS) and N‐isopropylacrylamide (NIPAAM) with different block lengths were prepared by atom transfer radical polymerization (ATRP). Controlled polymerization was achieved by using ethyl 2‐chloropropionate (ECP) as initiator and CuCl/CuCl₂/tris(2‐dimethylaminoethyl)amine (Me₆TREN) catalytic system in DMF:water 50:50 (v/v) mixtures at 20 °C. Blocks lengths ranging from 36 to 98 repeating units were obtained. The association properties in aqueous solutions at different NaCl ionic strengths were studied as a function of temperature and polymer concentration by dynamic light scattering, fluorescence spectroscopy, and energy‐filtered transmission electron microscopy. The block copolymers with a higher pNIPAAM/pAMPS ratio formed spherical core‐shell type micelles independently of the ionic strength. The block copolymers with lower pNIPAAM/pAMPS ratio formed core‐shell type micelles at high ionic strength. Larger particles were observed at low ionic strength, which could be due to the formation of vesicles or compound micelles/micellar clusters. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4830–4842, 2008