An introduction to hybrid ion trap/time‐of‐flight mass spectrometry coupled with liquid chromatography applied to drug metabolism studies

Abstract

Metabolism studies play an important role at various stages of drug discovery and development. Liquid chromatography combined with mass spectrometry (LC/MS) has become a most powerful and widely used analytical tool for identifying drug metabolites. The suitability of different types of mass spectrometers for metabolite profiling differs widely, and therefore, the data quality and reliability of the results also depend on which instrumentation is used. As one of the latest LC/MS instrumentation designs, hybrid ion trap/time-of-flight MS coupled with LC (LC-IT-TOF-MS) has successfully integrated ease of operation, compatibility with LC flow rates and data-dependent MS(n) with high mass accuracy and mass resolving power. The MS(n) and accurate mass capabilities are routinely utilized to rapidly confirm the identification of expected metabolites or to elucidate the structures of uncommon or unexpected metabolites. These features make the LC-IT-TOF-MS a very powerful analytical tool for metabolite identification. This paper begins with a brief introduction to some basic principles and main properties of a hybrid IT-TOF instrument. Then, a general workflow for metabolite profiling using LC-IT-TOF-MS, starting from sample collection and preparation to final identification of the metabolite structures, is discussed in detail. The data extraction and mining techniques to find and confirm metabolites are discussed and illustrated with some examples. This paper is directed to readers with no prior experience with LC-IT-TOF-MS and will provide a broad understanding of the development and utility of this instrument for drug metabolism studies.

Endohedral Clusterfullerenes: Future Perspectives

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Metabolism and Disposition of Aditoprim in Swine, Broilers, Carp and Rats

“…Isotopic tracing combined with online radioactivity detection and mass spectrometry is an effective modern analytical tool used to elucidate the metabolic and residue kinetics of the tested compounds in animals 19 . With its high resolution and mass accuracy, as well as reliable MS n capability, liquid chromatography/ion trap/time-of-flight mass spectrometry (LC/MS-IT-TOF) technology is being widely used for the identification of the structure of the unknown compounds 20 . In the present study, a stable 3 H-ADP was prepared by our group, and its metabolism, excretion, distribution, and elimination were systematically investigated in swine, broilers, carp, and rats after oral administration of 3 H-ADP (5 mg/kg b. w.) for a single or 7 days.…”

Trends in the application of high-resolution mass spectrometry for human biomonitoring: An analytical primer to studying the environmental chemical space of the human exposome

“…The distinct advantages of a QqTOF are fast acquisition rate, wide mass range and high ion transmission efficiency. A hybrid between TOF and ion trap mass analyzers was released as an IT-TOF, which can retain ions in the acceleration chamber for multi-stage mass spectrometry (MS n ) and switch polarity at a high speed (Liu, 2012). Among all the currently available HRMS platforms, TOF-MS and QqTOF MS are the most widely used systems for studying human exposures to environmental chemicals from an exposome perspective (Table 1), as detailed in the later section.…”