Liquid extraction surface analysis mass spectrometry (LESA‐MS) as a novel profiling tool for drug distribution and metabolism analysis: the terfenadine example
-
- Daniel Eikel
- Advion Inc. Ithaca NY 14850 USA
-
- Marissa Vavrek
- Merck Research Laboratories Preclinical Drug Metabolism Pharmacokinetics West Point PA 19486 USA
-
- Sheri Smith
- Merck Research Laboratories Preclinical Drug Metabolism Pharmacokinetics West Point PA 19486 USA
-
- Carol Bason
- Merck Research Laboratories Preclinical Drug Metabolism Pharmacokinetics West Point PA 19486 USA
-
- Suzie Yeh
- Merck Research Laboratories Preclinical Drug Metabolism Pharmacokinetics West Point PA 19486 USA
-
- Walter A. Korfmacher
- Consultant Westfield NJ 07090 USA
-
- Jack D. Henion
- Advion Inc. Ithaca NY 14850 USA
抄録
<jats:p>Liquid extraction surface analysis mass spectrometry (LESA‐MS) is a novel surface profiling technique that combines micro‐liquid extraction from a solid surface with nano‐electrospray mass spectrometry. One potential application is the examination of the distribution of drugs and their metabolites by analyzing <jats:italic>ex vivo</jats:italic> tissue sections, an area where quantitative whole body autoradiography (QWBA) is traditionally employed. However, QWBA relies on the use of radiolabeled drugs and is limited to total radioactivity measured whereas LESA‐MS can provide drug‐ and metabolite‐specific distribution information. Here, we evaluate LESA‐MS, examining the distribution and biotransformation of unlabeled terfenadine in mice and compare our findings to QWBA, whole tissue LC/MS/MS and MALDI‐MSI. The spatial resolution of LESA‐MS can be optimized to ca. 1 mm on tissues such as brain, liver and kidney, also enabling drug profiling within a single organ. LESA‐MS can readily identify the biotransformation of terfenadine to its major, active metabolite fexofenadine. Relative quantification can confirm the rapid absorption of terfendine after oral dosage, its extensive first pass metabolism and the distribution of both compounds into systemic tissues such as muscle, spleen and kidney. The elimination appears to be consistent with biliary excretion and only trace levels of fexofenadine could be confirmed in brain. We found LESA‐MS to be more informative in terms of drug distribution than a comparable MALDI‐MS imaging study, likely due to its favorable overall sensitivity due to the larger surface area sampled. LESA‐MS appears to be a useful new profiling tool for examining the distribution of drugs and their metabolites in tissue sections. Copyright © 2011 John Wiley & Sons, Ltd.</jats:p>
収録刊行物
-
- Rapid Communications in Mass Spectrometry
-
Rapid Communications in Mass Spectrometry 25 (23), 3587-3596, 2011-11-16
Wiley
- Tweet
詳細情報 詳細情報について
-
- CRID
- 1361981469752026496
-
- DOI
- 10.1002/rcm.5274
-
- ISSN
- 10970231
- 09514198
-
- データソース種別
-
- Crossref