Véronique Gobry

Microfabricated polymer injector for direct mass spectrometry coupling

This paper demonstrates the coupling of a plasma etched polymer microfluidic system with an electrospray mass spectrometer by generation of a nanospray. Taking advantage of the microtechnology processes and polymer properties, high volume production with good reproducibility of hydrophobic interfaces could be obtained. The nanospray was directly produced from the outlet of the plastic microfabricated chip positioned in front of the capillary entrance of the mass spectrometer. No chemical background due to the polymer has been observed under standard nanospray conditions. The performances of the spray as well as its efficiency have been demonstrated by flow measurements, stability establishment and tandem mass spectrometry experiment on angiotensin II. The spray was actuated without additional flow in methanol: water:acetic acid (50:49:1%) solution. A 40 fmol/νL detection limit could be reached.

Lipophilicity and solvation of anionic drugs

This paper first gives a brief review of the main techniques used to measure the lipophilicity of neutral and ionic drugs, namely the shake-flask method, potentiometry, and cyclic voltammetry at liquid-liquid interfaces. The lipophilicity of 28 acidic compounds with various functional groups was studied by potentiometry and cyclic voltammetry in the n-octanol/water and 1,2-dichloroethane/water systems in order to complement our understanding of the lipophilicity of neutral and ionized acids and to clarify the solvation mechanisms responsible for their partition. The parameter diff (log P(N-A)(dce)) (i.e., log P of the neutral acid minus standard log P of the conjugated anion in 1,2-dichloroethane/water) was shown to depend not only on intramolecular interactions and conformational effects in the neutral and anionic forms, but also on the delocalization of the negative charge in the anion, confirming the ability of Borns solvation model to describe qualitatively the effect of the molecular radius on the lipophilicity of ions.

Theoretical and Experimental Exploration of the Lipophilicity of Zwitterionic Drugs in the 1,2-Dichloroethane/Water System

AbstractPurpose. This work examines the lipophilic behavior of various zwitterions and shows how distribution profiles in biphasic systems and ionic partition diagrams may improve our understanding of pH-absorption profiles of drugs. Methods. The lipophilicity of various zwitterionic drugs was examined by potentiometry and cyclic voltammetry in the 1,2-dichloroethane/water system to study the intramolecular interactions and conformational effects affecting absorption and activity of zwitterions, as well as to draw their theoretical and experimental ionic partition diagrams. Results. Different theoretical partition diagrams are reported according to the tautomeric constant of the zwitterion. Shifts of apparent pKa are obtained in the ionic partition diagrams of raclopride and eticlopride and compared to the deviations from pH-absorption profile described in the literature for lipophilic drugs. The physicochemical origin of these shifts is discussed. Conclusions. The comparison between pH-absorption profiles and ionic partition diagrams of zwitterions is shown here to be of value for a better mechanistic understanding of absorption processes, thus opening new perspectives in studying pH-absorption profiles of ionizable drugs.

Integration of a membrane-based desalting step in a microfabricated disposable polymer injector for mass spectrometric protein analysis

A simple desalting procedure for the coupling of a polymer microchip injector to mass spectrometry is proposed. The overall process is based on the adsorption of proteins on a poly(vinylidene difluoride) (PVDF) membrane, which are then directly eluted in the spraying solution. This microchip‐based approach has been successfully applied to small drugs, peptides and proteins originally diluted in phosphate‐buffered saline (PBS). Moreover, when eluting the retained proteins in small volumes, a preconcentration is obtained. The combination of single‐use, mass‐produceable, low‐sample‐consumption, easy‐to‐automate, miniaturized polymer injectors with easy‐to‐handle solution‐exchange membranes makes this system particularly amenable to screening applications.

The Apparent Lipophilicity of Quaternary Ammonium Ions Is Influenced by Galvani Potential Difference, Not Ion-Pairing: A Cyclic Voltammetry Study

AbstractPurpose. This work examines whether ion–pairing contributes to the apparent lipophilicity of cations, which is seen by a shake–flask or titrimetic method to be influenced by the nature and concentration of counter–ions. Methods. To solve this problem, the lipophilicity of several quaternary ammonium drugs was measured by cyclic voltammetry in the 1,2–dichloroethane/water system. The standard ionic partition coefficient values so obtained (log P°,Cdce) were correlated with log Poct values calculated by the CLOGP algorithm for the respective neutral molecules. Results. The standard (i.e., intrinsic) lipophilicity values are shown to depend on a, the structure of the ion (nature, volume, charge), and b, on the Galvani potential difference at the ITIES (interface between two immiscible electrolyte solutions). Conclusions. The standard lipophilicity values were not influenced by counter–ions. In contrast, simulations showed that the increased apparent lipophilicity of cations, as measured by the shake–flask method in the presence of lipophilic anions, is fully accounted for by the resulting increase in the Galvani potential difference.

Ionic partition diagram of the zwitterionic antihistamine cetirizine

Reference LEPA-ARTICLE-2001-013doi:10.1002/1522-2675(20010228)84:2 3.0.CO;2-4 Record created on 2005-11-07, modified on 2017-05-12

Protein Analyses with Electrochemical and Nanoelectrospray Detection on Disposable Plastic Microchips

The development of µ-total analysis systems for proteomics faces features that are specific to the diversity in protein properties such as hydrophobicity and heterogeneity. Particular problems such as non specific adsorption on the capillary walls (glass or plastics) or the use of surfactants or solvent mixtures render the use of electrokinetic pumping and free flow electrophoresis more problematic than in DNA analyses. Therefore, we developed concepts where disposable chips are fabricated with various properties and where the chips are functionalised for affinity or chromatography purposes with electrochemical or mass spectrometry detection. Finally, a novel sub-nL injection method without electrokinetic means has been developed in order to enable the integration of injector, separation channel and detector on a single µ-chip.