Exhaled breath condensate: Determination of non-volatile compounds and their potential for clinical diagnosis and monitoring. A review

Exhaled breath condensate is a promising, non-invasive, diagnostic sample obtained by condensation of exhaled breath. Starting from a historical perspective of early attempts of breath testing towards the contemporary state-of-the-art breath analysis, this review article focuses mainly on the progress in determination of non-volatile compounds in exhaled breath condensate. The mechanisms by which the aerosols/droplets of non-volatile compounds are formed in the airways are discussed with methodological consequences for sampling. Dilution of respiratory droplets is a major problem for correct clinical interpretation of the measured data and there is an urgent need for standardization of EBC. This applies also for collection instrumentation and therefore various commercial and in-house built devices are described and compared with regard to their design, function and collection parameters. The analytical techniques and methods for determination of non-volatile compounds as potential markers of oxidative stress and lung inflammation are scrutinized with an emphasis on method suitability, sensitivity and appropriateness. The relevance of clinical findings for each group of possible non-volatile markers of selected pulmonary diseases and methodological recommendations with emphasis on interdisciplinary collaboration that is essential for future development into a fully validated clinical diagnostic tool are given.     

Solid-phase synthesis of a library of C-terminal agmatine dipeptides using a backbone amide linker (BAL) strategy

In this Letter, we report a novel solid-phase strategy using a backbone amide linker (BAL) attached to a polystyrene support for the synthesis of C-terminal agmatine dipeptides. Our method eliminates the need to purify intermediates by column chromatography and enables us to build rapidly an 18-member library of C-terminal agmatine dipeptides which are subsequently screened for inhibitory activity against a viral enzyme.     

Generation of 25 ps pulses by self induced mode locking of a single broad area diode laser with 300 mW average output power

Detailed investigations of the spatiotemporal and spectral emission properties of a high power diode laser are presented. The AR coated laser diode with design wavelength of 940 nm is driven in an external resonator. The laser generates up to 340 mW average output power in a train of picosecond pulses with durations of 25 ps and repetition rates of 2.6 GHz. The mechanism of mode locking is discussed as self pulsation because of the strong correlation between round trip time and repetition rate. The double-sided exponential pulses suggest saturable absorber action.     

Solid-phase synthesis of neuroactive spider-wasp hybrid toxin analogues using a backbone amide linker

Polyamine toxins isolated from the venoms of spiders and wasps and their synthetic analogues are uncompetitive antagonists of ligand-gated ionotropic receptors in the central- and peripheral nervous systems, and have proved valuable as tools for the investigation of receptor structure and function. In the present letter we describe the efficient solid-phase synthesis (SPS) of novel hybrid toxins using a BAL resin. This strategy enables the bidirectional construction of toxin molecules and has a potential in SPS of chemically diverse libraries of toxin analogues for structure-activity relationship (SAR) studies.     

(Z)-2-(2-三苯甲基氨基噻唑-4-基)-2-[1,5-二(二苯甲氧基)-4-吡啶酮-2-基甲氧基亚胺]乙酸的合成工艺改进

以5-羟基-2-羟甲基-4-吡喃酮为原料,经羟基保护、迈克尔加成、亲核取代、Mitsunobu反应、肼解及缩合等反应合成了BAL30072关键中间体——(Z)-2-(2-三苯甲基氨基噻唑-4-基)-2-(1,5-二(二苯甲氧基)-4-吡啶酮-2-基甲氧基亚胺)乙酸,总收率23%,其结构经1H NMR和MS确证。该合成工艺已放大到公斤级规模。     

Validation of a new HPLC‐UV method for determination of the antibiotic linezolid in human plasma and in bronchoalveolar lavage

A rapid and selective HPLC‐UV method was developed for the quantification of linezolid (LNZ) in human plasma and bronchoalveolar lavage (BAL) at the concentrations associated with therapy. Plasma samples were extracted by solid‐phase extraction followed by evaporation to dryness and reconstitution in mobile phase solution. The chromatographic separation was carried out on a C₁₈ column with an isocratic mobile phase consisting of dihydrogen phosphate buffer 50 mm (pH 3.5) and acetonitrile (60:40 v/v). The detection was performed using a photodiode array. Under these conditions, a single chromatographic run could be completed within 12 min. The method was validated by estimating the precision and the accuracy for inter‐ and intra‐day analysis in the concentration range of 25–25600 ng/mL. The method was linear over the investigated range with all the correlation coefficients R > 0.999. The intra‐ and inter‐day precision was within 8.90% and the accuracy ranged from ?4.76 to +5.20%. This rapid and sensitive method was fully validated and could be applied to pharmacokinetic study for the determination of LNZ levels in human plasma and BAL samples. Copyright © 2013 John Wiley & Sons, Ltd.