Rapid quantification of HIV protease inhibitors in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry

HIV protease inhibitors are important antiretroviral drugs which have substantially reduced the morbidity and mortality associated with HIV-1 infection. Recent data have shown relationships between plasma concentrations of the protease inhibitors and clinical response, which makes therapeutic drug monitoring valuable. We have developed and validated an assay, using liquid chromatography coupled with electrospray tandem mass spectrometry (LC/MS/MS), for the routine quantification of the six licensed protease inhibitors (amprenavir, indinavir, lopinavir, nelfinavir, ritonavir and saquinavir) and the pharmacologically active nelfinavir metabolite M8 in plasma. The sample pretreatment consisted of protein precipitation with a mixture of methanol and acetronitrile using only 100 microl of plasma. Chromatographic separation was performed on an Inertsil ODS3 column (50 x 2.0 mm i.d., particle size 5 microm), with a quick stepwise gradient using an acetate buffer (pH 5) and methanol, at a flow rate of 0.5 ml min(-1). The analytical run time was 5.5 min. The use of a 96-well plate autosampler allowed batch sizes up to 150 patient samples. The triple-quadrupole mass spectrometer was operated in the positive ion mode and multiple reaction monitoring was used for drug quantification. The method was validated over the concentration ranges 0.01-10 microg ml(-1) for indinavir and saquinavir, 0.1-10 microg ml(-1) for amprenavir, 0.05-10 microg ml(-1) for nelfinavir and ritonavir, 0.1-20 microg ml(-1) for lopinavir and 0.01-5 microg ml(-1) for M8. Saquinavir-d(5) and indinavir-d(6) were used as internal standards. The coefficients of variation were always <10% for both intra-day and inter-day precisions for each compound. Mean accuracies were also between the designated limits (+/-15%). The validated concentration ranges proved to be adequate in daily practice. This robust and fast LC/MS/MS assay is now successfully applied for routine therapeutic drug monitoring and pharmacokinetic studies in our hospital.     

Ion Pairing in Protic Ionic Liquids Probed by Far‐Infrared Spectroscopy: Effects of Solvent Polarity and Temperature

The cation–anion and cation–solvent interactions in solutions of the protic ionic liquid (PIL) [Et₃NH][I] dissolved in solvents of different polarities are studied by means of far infrared vibrational (FIR) spectroscopy and density functional theory (DFT) calculations. The dissociation of contact ion pairs (CIPs) and the resulting formation of solvent‐separated ion pairs (SIPs) can be observed and analyzed as a function of solvent concentration, solvent polarity, and temperature. In apolar environments, the CIPs dominate for all solvent concentrations and temperatures. At high concentrations of polar solvents, SIPs are favored over CIPs. For these PIL/solvent mixtures, CIPs are reformed by increasing the temperature due to the reduced polarity of the solvent. Overall, this approach provides equilibrium constants, free energies, enthalpies, and entropies for ion‐pair formation in trialkylammonium‐containing PILs. These results have important implications for the understanding of solvation chemistry and the reactivity of ionic liquids.     

Auf eine Gefahr bei der Trennung von Mineralien mittels schwerer L?sungen

Ohne Zusammenfassung     

Scaling properties of a tetragonal photonic crystal design having a large complete bandgap

Photonic crystal structures (PCs) of tetragonal lattice type are introduced and studied. They feature complete three-dimensional (3D) photonic bandgaps (PBGs). The PC design is based on two systems of ordered, parallel pores being perpendicular to each other. For increasing pore radii, the pore systems interpenetrate and an inverted woodpile geometry arises. The size of the 3D bandgaps depends on the ratio of the cell parameters L_x, L_y, and L_z, the pore radii and the refractive index of the dielectric material. If realized as a silicon/air structure, the maximum 3D gap is larger than 25%. A possible fabrication route for the near-infrared is based on 2D macroporous silicon where perpendicular pores are drilled, e.g., by focused-ion-beam etching. The dispersion behaviour of the PCs is theoretically analysed (band structures, density-of-states), systematically varying all relevant parameters. The optimization of the PBG sizes as well as a possible tunability of the PBG energies are discussed.     

Recent developments in the total synthesis of fungicidal natural products--a crop protection perspective

Natural products play an important role as lead structures for the identification of novel active ingredients in crop protection. As it is the case in the pharmaceutical industry, however, many crop protection companies have substantially decreased their in-house efforts in natural product exploration. Therefore, joint projects with academic research groups become more and more important in the field. This review describes several examples for successful collaborations in the field of fungicidal natural products.     

Zur Bestimmung des Titans

Analytical and Bioanalytical Chemistry -