A quantitative LC/MS method targeting urinary 1-methyl-4-imidazoleacetic acid for safety monitoring of the global histamine turnover in clinical studies

Anaphylaxis is a potentially life-threatening condition triggered mainly by the release of inflammatory mediators, notably histamine. In pharmaceutical research, drug discovery, and clinical evaluation, it may be necessary to accurately assess the potential of a compound, event, or disorder to promote the release of histamine. In contrast to the measurement of plasma histamine, determination of the stable metabolite 1-methyl-4-imidazoleacetic acid (tele-MIAA) in urine provides a noninvasive and more reliable methodology to monitor histamine release. This study presents a repeatable high-performance liquid chromatography coupled to electrospray mass spectrometry (LC–ESI–MS) method where tele-MIAA is baseline separated from its structural isomer 1-methyl-5-imidazoleacetic acid (pi-MIAA) and an unknown in human urine. The ion-pairing chromatography method, in reversed-phase mode, based on 0.5 mM tridecafluoroheptanoic acid demonstrated high repeatability and was applied in a clinical development program that comprised a large number of clinical samples from different cohorts. The inter- and intra-run precision of the method for tele-MIAA were 8.4 and 4.3 %, respectively, at the mean urinary concentration level, while method accuracy was between ?16.2 and 8.0 % across the linear concentration range of 22–1,111 ng mL^?1. Overall, method precision was greater than that reported in previously published methods and enabled the identification of gender differences that were independent of age or demography. The median concentration measured in female subjects was 3.0 μmol mmol^?1 of creatinine, and for male subjects, it was 2.1 μmol mmol^?1 of creatinine. The results demonstrate that the method provides unprecedented accuracy, precision, and practicality for the measurement of tele-MIAA in large clinical settings.

The effect of ply properties in paperboard converting operations: a way to increase formability

Cellulose - This study addresses the question of how the difference in mechanical properties of the individual layers in a multi-ply commercial paperboard affects the outcome of the tray-forming...     

Potential of coded excitation in medical ultrasound imaging

Improvement in signal-to-noise ratio (SNR) and/or penetration depth can be achieved in medical ultrasound by using long coded waveforms, in a similar manner as in radars or sonars. However, the time-bandwidth product (TB) improvement, and thereby SNR improvement is considerably lower in medical ultrasound, due to the lower available bandwidth. There is still space for about 20 dB improvement in the SNR, which will yield a penetration depth up to 20 cm at 5 MHz [M. O'Donnell, IEEE Trans. Ultrason. Ferroelectr. Freq. Contr., 39(3) (1992) 341]. The limited TB additionally yields unacceptably high range sidelobes. However, the frequency weighting from the ultrasonic transducer's bandwidth, although suboptimal, can be beneficial in sidelobe reduction. The purpose of this study is an experimental evaluation of the above considerations in a coded excitation ultrasound system. A coded excitation system based on a modified commercial scanner is presented. A predistorted FM signal is proposed in order to keep the resulting range sidelobes at acceptably low levels. The effect of the transducer is taken into account in the design of the compression filter. Intensity levels have been considered and simulations on the expected improvement in SNR are also presented. Images of a wire phantom and clinical images have been taken with the coded system. The images show a significant improvement in penetration depth and they preserve both axial resolution and contrast.     

Conditions for sulfite stabilization and determination by ion chromatography

The efficiencies of three groups of potential sulfite-stabilizing compounds were found to be in the order: carbonyls > alcohols = saccharides. A mole ratio of 1:1 between formaldehyde and sulfite was sufficient for stabilizing a sulfite solution for at least 72 h. The lower stabilizing efficiencies of the alcohols and saccharides examined could be compensated by using large excesses of these compounds. For example, if a 100-fold excess of glycerol over sulfite was used, the recovery of sulfite was 96% after 72 h compared with only 40% without addition of stabilizer. During separations by ion chromatography, almost no oxidation of the sample occurs provided the sample solution is directly injected into a deaerated eluent. For formaldehyde, the peak heights were found to depend on the molar ratio of the stabilizer to sulfite as well as on the concentration of sulfite. This effect was not found for the other stabilizers tested.     

Automatic coulometric titration with photometric end-point detection : Part I. A coulometric titrator based on differential photometric detection

A system for automatic coulometric titrations with photometric end-point detection is described. To compensate for errors caused by gas bubbles and turbidity, the beam is split after passing the titration cell. The intensities of the respective light beams are registered by means of two photodiodes operating in the current mode. The currents are converted to voltages and the logarithm of the quotient is taken. The measured absorbance is only slightly dependent on the variation in the intensity of the incident light. A diminution of one absorbance unit causes a relative error of less than 5%. The deviations due to carbon particles (37–75 μm) were less than 0.002 absorbance units per mg of carbon present in 10 ml of solution. The improvement with respect to errors caused by gas bubbles is illustrated. The fundamental advantage of a one-lamp system over a twolamp system is shown.     

Single-frequency operation of a high-power, long-wavelength semiconductor disk laser

An optically pumped, high-power, single-frequency semiconductor disk laser is demonstrated. A thin (50 microm) diamond bonded to an InGaAsP gain chip provides the combined functions of heat removal and spectral filtering, thus eliminating the need for the additional intracavity etalons that are usually employed for single-frequency operation. In a short cavity (4 mm) configuration we obtained a maximum output power of 470 mW at 0 degrees C and 170 mW at 20 degrees C in a near-diffraction-limited beam (M2 < 1.2). The emission wave-length was 1549 nm and the linewidth was less than 200 MHz.     

Thio arsenosugars identified as natural constituents of mussels by liquid chromatography-mass spectrometry

Two novel thio arsenosugars have been identified by liquid chromatography-mass spectrometry as significant arsenic constituents in samples of mussels.     

High-throughput screening of pKa values of pharmaceuticals by pressure-assisted capillary electrophoresis and mass spectrometry

A high-throughput pKa screening method based on pressure-assisted capillary electrophoresis (CE) and mass spectrometry (MS) is presented. Effects of buffer type and ionic strength on sensitivity and pKa values were investigated. Influence of dimethyl sulfoxide (DMSO) concentration present in the sample on effective mobility measurement was examined. A series of ten volatile buffers, covering a pH range from 2.5 to 10.5 with the same ionic strength, was employed. The application of volatile background electrolytes resulted in significant signal increase as compared with commonly used non-volatile phosphate buffers. In general, the CE/MS system provided a ten-fold higher sensitivity than conventional UV detection. The newly developed CE/MS method offers high-throughput capacity by pooling a number of compounds into a single sample. Simultaneous measurement of more than 50 compounds was readily achieved in less than 150 min. The measured pKa values are consistent with the published data obtained from the CE/UV method and are also in good agreement with data generated by other methods. Other advantages of using CE/MS for pKa screening are illustrated with typical examples, including poorly soluble compounds and non-UV-absorbing compounds.