Application of dried spot cards as a rapid sample treatment method for determining hydroxytyrosol metabolites in human urine samples. Comparison with microelution solid-phase extraction

Two different rapid sample pretreatment strategies, dried spot cards, and microelution solid-phase extraction plates (μSPE), with ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) have been developed and validated for the determination of hydroxytyrosol and its metabolites in spiked human urine samples. Hydroxytyrosol, hydroxytyrosol-3′-O-glucuronide, hydroxytyrosol-4′-O-glucuronide, hydroxytyrosol-3-O-sulphate, and homovanillic alcohol-4′-O-glucuronide were used as the target compounds. Using the FTA DMPK-A dried urine spot card under optimum conditions, with 5 μL of preconcentrated urine volume and 100 μL of methanol/water (50/50, v/v) as the elution solvent, the extraction recovery (%R) of the compounds studied was higher than 80 %, and the matrix effect (%ME) was less than 8 %. The stability of these cards and punching at the centre or side of the card were also studied, obtaining an excellent stability after 7 days of storage and complete homogeneity across the surface of the dried drop. The different μSPE parameters that affect the efficiency were also studied, and under optimum conditions, the %R and the %ME were higher than 70 % and lower than 17 %, respectively. The linearity range in dried urine spot cards was 2.5-20 μM for all the metabolites, with the exception of hydroxytyrosol-3-O-sulphate and hydroxytyrosol, which were 0.3-70 μM and 2.5-50 μM respectively. With regards to μSPE, the linearity range was 0.5-5 μM for all the studied compounds, except for hydroxytyrosol-3-O-sulphate, which was 0.08-5 μM. The quantification limits (LOQs) were 0.3-2.5 μM and 0.08-0.5 μM in dried spot cards and in μSPE, respectively. The two developed methods were then applied and compared for determining hydroxytyrosol and its metabolites in human 24 h-urine samples after a sustained consumption (21 days) of a phenol-enriched virgin olive oil. The metabolites identified were hydroxytyrosol in its glucuronide and sulphate forms, homovanillic alcohol in its glucuronide and sulphate forms, homovanillic acid sulphate and hydroxytyrosol acetate sulphate.     

Surface measures in Carnot-Carathéodory spaces

In the framework of Carnot-Carathéodory spaces we study Minkowski content and perimeter, we prove some coarea formulas, and finally we prove some variational approximations of the perimeter. Received May 30, 2000 / Accepted October 10, 2000 / Published online December 8, 2000     

FTIR/ATR study of the copolymerization of diglycidyl ether of Bisphenol A with methyl-substituted γ-lactones catalyzed by rare earth triflate initiators

Mixtures of DGEBA with γ-valerolactone (γ-VL) or α-methyl-γ-butyrolactone (γ-MBL) 2:1 (mol/mol) were cationically copolymerized in the presence of scandium, ytterbium, or lanthanum triflates as initiators. The evolution of the different reactive groups was followed by means of FTIR/ATR spectroscopy. From these experiments, we could detect the coexistence of two unexpected processes: a reversion of the intermediate spiroorthoester formed to the initial products and a depolymerization process, which only takes place in samples with γ-VL, when scandium triflate was used as initiator or when the proportion of ytterbium triflate was increased from 1 to 3 phr. When γ-MBL was used as comonomer no depolymerization occurs which supports the proposed mechanism. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 45: 2129–2141, 2007     

Far-infrared response of quantum-dot molecules

We report an analysis of the dipole response of a symmetric quantum-dot molecule as a function of the dot-dot separation and intensity of a perpendicular magnetic field. The potential barrier is assumed proportional to the interdot distance using a two-center oscillator potential. The results are obtained within the symmetry-unrestricted TDLSDA. It is shown that the FIR details, specially the fragmentation of the low-energy brach, are quite sensitive to the interdot separation and that in both the small and large separation limits the results converge towards the analytic Kohn's magnetoplasmon energies. The validity of the LSDA is checked by comparison with the Hartree-Fock dipole spectrum in one case. Received 29 November 2000     

First total synthesis of versicotide D and analogs

The first total synthesis of cyclotetrapeptide versicotide D has been achieved in 21% overall yield using solid phase peptide synthesis and solution cyclization. In addition, in the search for candidates of antimalarial new drugs, one cyclic tetrapeptide analog which differs in the sequence, and four cyclic pentapeptide containing N-methyl amino acids, were prepared. The obtained compounds were evaluated against P. falciparum 3D7. Versicotide D showed low micromolar antiplasmodial activity.     

Non-linear protocell models: synchronization and chaos

We consider generic protocells models allowing linear and non-linear kinetics for the main involved chemical reactions. We are interested in understanding if and how the protocell division and the metabolism do synchronise to give rise to sustainable evolution of the protocell.