Abstract

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 mu mol mmol(-1) of creatinine, and for male subjects, it was 2.1 mu mol 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.

Keywords

tele-MIAA; HILIC; Ion-pairing chromatography; Ion suppression; LC/MS; Clinical biomarker

Published in

Analytical and Bioanalytical Chemistry
2014, Volume: 406, number: 6, pages: 1751-1762
Publisher: SPRINGER HEIDELBERG

SLU Authors

• Moritz, Thomas

  • Department of Forest Genetics and Plant Physiology, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Biochemistry and Molecular Biology
Analytical Chemistry


Publication identifier

DOI: https://doi.org/10.1007/s00216-013-7594-6

Permanent link to this page (URI)

https://res.slu.se/id/publ/67668