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.

In situ mass spectrometry imaging and ex vivo characterization of renal crystalline deposits induced in multiple preclinical drug toxicology studies.

Drug toxicity observed in animal studies during drug development accounts for the discontinuation of many drug candidates, with the kidney being a major site of tissue damage. Extensive investigations are often required to reveal the mechanisms underlying such toxicological events and in the case of crystalline deposits the chemical composition can be problematic to determine. In the present study, we have used mass spectrometry imaging combined with a set of advanced analytical techniques to characterize such crystalline deposits in situ.

Determination of specific radioactivity for (76)Br-labeled compounds measuring the ratio between (76)Br and (79)Br using packed capillary liquid chromatography mass spectrometry.

Packed capillary liquid chromatography with electrospray mass spectrometry was used for direct determination of the specific radioactivity by calculation of isotope ratios between the (76)Br- and (79)Br-labeled analogues of N-((3-aminomethyl)benzyl)-4-bromobenzamide. Using 20 microL injections on packed capillary columns, sufficient mass sensitivity was attained for the determination on an injected amount of radioactivity corresponding to approximately 2 MBq (0.3 pmol of the (76)Br isotopic analogue).

Determination of raclopride in human plasma by on-column focusing packed capillary liquid chromatography-electrospray ionisation mass spectrometry.

A packed capillary liquid chromatography-electrospray ionisation mass spectrometry method was developed for the quantitative determination of raclopride in human plasma samples. Plasma samples containing the drug and its isotopically substituted analogue (2H3)raclopride as internal standard were extracted on solid-phase extraction discs, evaporated and reconstituted in a solvent with less elution strength than the mobile phase. Packed capillary columns of 100 mm x 500 microm I.

Reversed-phase ion-pair chromatography coupled to electrospray ionisation mass spectrometry by on-line removal of the counter-ions.

A strong anion-exchanger was used as a trapping column to perform on-line coupling of ion-pair chromatography with electrospray ionisation mass spectrometry. Ion-pairing reagents were used to retain polar analytes of low molecular mass away from the solvent front in reversed-phase LC. The trapping column enabled removal of the non-volatile counter-ions from the mobile phase prior to detection, so that the electrospray process could be performed with favourable ionisation conditions and without contamination of the interface.

Compounds labelled with short-lived beta(+)-emitting radionuclides and some applications in life sciences. The importance of time as a parameter.

Some examples of recent development of the synthesis of compounds labelled with short-lived beta(+)-emitting radionuclides will be discussed with an emphasis on the importance of time in selecting a synthetic strategy. Furthermore the use of such labelled compounds to monitor certain processes in areas within the field of analytical chemistry and in various applications in drug development will be presented.