Current applications of high-resolution mass spectrometry in drug metabolism studies

Abstract

This paper reviews high-resolution mass spectrometry (HRMS) approaches published in 2007-2011 for the elucidation of drug metabolism with a focus on new therapeutics, new drugs of abuse, and doping agents using time-of-flight, single-stage Orbitrap, ion trap Orbitrap, and other Fourier transform MS-based techniques. The present review provides an overview of metabolite-generating systems and assays used, sample preparation techniques, ionization and fragmentation techniques, as well as data mining strategies and software tools which were used in the reviewed papers. Furthermore, HRMS-specific topics such as demand for a certain resolution or a specific mass accuracy are discussed in detail and corresponding recommendations are given. Finally, the advantages and limitations of these methods are discussed.

Analytical Methods for Quantification of Drug Metabolites in Biological Samples

“…On the other hand, Orbitrap analyzers provide a resolving power of up to 100,000 with mass accuracy below 1 ppm. FT-ICR analyzers provide ultrahigh mass resolving power greater than 200,000 but high purchasing and maintenance cost are beyond financial capabilities of most routine laboratories [27].…”

“…A short overview of analytical strategies for identification of metabolites will be provided. More information regarding metabolite identification can be found in following review articles [7,[23][24][25][26][27]. The selection of suitable LC-MS instrumentation is needed for qualitative evaluation of metabolites.…”

Current applications of high-resolution mass spectrometry for the analysis of new psychoactive substances: a critical review

“…The first publication describing the use of HRMS for the analysis of NPS was in 2010 regarding the metabolism of 3,4-methylenedioxypyrovalerone (MPDV) published by Meyer et al [13] and was followed by an increasing number of publications each year with a total of 25 publications identified in 2016, double the number published in 2015 ( Figure S1 in the Electonic Supplementary Material). The increasing use of HRMS has been highlighted by several reviews, mostly focusing on the role of this technique in forensic and clinical toxicology [14][15][16]. Recently, Maurer et al [17] reviewed the use of HRMS in toxicology and attributed its increased popularity to factors such as the ability to differentiate compounds with identical nominal masses but different accurate masses and the ease at which new compounds can be added to already existing screening procedures.…”

“…Finally, the use of HRMS in metabolism studies has increased in recent years particularly due to the sophisticated software tools available [14]. Peters et al [20] reviewed the recent developments of LC-MS for metabolism studies of NPS identifying that the main advantage of HRMS is the elimination of interferences that have the same nominal mass but different accurate masses.…”

Assessment of the Occurrence and Potential Risks of Antibiotics and their Metabolites in South Florida Waters Using Liquid Chromatography Tandem Mass Spectrometry

“…In recent years, the advent of hybrid high resolution mass spectrometers, such as quadrupole time of flight (QTOF), triple quadrupole time of flight (QqTOF), Fourier transform ion cyclotron resonance (FTICR), Orbitrap, and linear ion trap-Orbitrap (LTQOrbitrap), with elevated resolution (>40,000) and high mass accuracy (<5ppm) capabilities, has made the conditions ideal for screening and positive confirmation of unknown metabolites and transformation products both in metabolic profiling and environmental studies (Stolker et al, 2004;Gros et al, 2009;Ferrer and Thurman, 2012;Hernandez et al, 2012;Meyer and Maurer, 2012;Qian et al, 2012). Limitations for the use of TOF instruments are less linear dynamic range (<10 3 ) and the need for internal calibration (for each pre and post sample injection) to maintain high mass accuracy (Hernandez et al, 2012).…”