Mass spectrometric characterization of efaproxiral (RSR13) and its implementation into doping controls using liquid chromatography–atmospheric pressure ionization‐tandem mass spectrometry

Thevis, Mario; Krug, Oliver; Schänzer, Wilhelm

doi:10.1002/jms.993

Cited by 17 publications

(14 citation statements)

References 16 publications

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“…Negative ion ESI MS/MS on an LTQ-Orbitrap has also been used to develop screening assays for performance enhancing chemicals such as efaproxiral (Thevis, Krug, & Schänzer, 2006c) and selective androgen receptor modulators (Thevis, Kamber, & Schänzer, 2006b). Figure 30 shows the LTQ-Orbitrap MS 2 and MS 3 spectra of efaproxiral for both ion polarities.…”

Section: B Metabolomicsmentioning

confidence: 99%

“…Mass accuracies of the dominant fragment ions range from 0.5 to 1.2 ppm and 1.0 to 5.9 ppm in positive and negative modes, respectively. The high performance features of the orbitrap coupled with the MS n capability of the LIT facilitated elucidation of the fragmentation pathway in both polarities, thereby allowing introduction of efaproxiral into an existing screening procedure for doping controls (Thevis, Krug, & Schänzer, 2006c).…”

Section: B Metabolomicsmentioning

confidence: 99%

“…The LTQOrbitrap has also been used to analyze intact small (3-10 kDa) (Bredehöft, Schänzer, & Thevis, 2008;Thevis et al, 2006a;Thevis, Thomas, & Schänzer, 2008b), medium (10-25 kDa) (Macek et al, 2006;Waanders, Hanke, & Mann, 2007) and large ($150 kDa) (Zhang & Shah, 2007) proteins where the MS n capability of the LIT coupled with the high performance features of the orbitrap can facilitate unambiguous determination of the charge states of fragment ions, as well as identification of PTMs by database searching. The high performance attributes of this hybrid mass spectrometer have also found applications in environmental chemistry (Barceló & Petrovic, 2007;Krauss & Hollender, 2008), drug and metabolite analysis (Breitling, Pitt, & Barrett, 2006;Cuyckens et al, 2008;Ding et al, 2007;Karu et al, 2007;Li et al, 2007a;Lim et al, 2007Lim et al, , 2008Madalinski et al, 2008;Nielen et al, 2007;Peterman et al, 2006;Ruan et al, 2008;Thevis et al, 2005;Thevis, Kamber, & Schänzer, 2006b;Thevis, Krug, & Schänzer, 2006c;Thevis et al, 2006dThevis et al, ,e, 2007aThevis et al, , 2008aZhu et al, 2007), lipidomics (Davis et al, 2008;Ejsing et al, 2006;Schwudke et al, 2007;Silipo et al, 2008), small-molecule (Chen et al, 2007b) and reaction product (Jamin et al, 2007) identification, as well as molecular structure characterization using hydrogen/deuterium exchange measurements (Chen et al, 2007a;...…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Orbitrap mass spectrometry: Instrumentation, ion motion and applications

Perry

Cooks

Noll

2008

Mass Spectrometry Reviews

406

290

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Since its introduction, the orbitrap has proven to be a robust mass analyzer that can routinely deliver high resolving power and mass accuracy. Unlike conventional ion traps such as the Paul and Penning traps, the orbitrap uses only electrostatic fields to confine and to analyze injected ion populations. In addition, its relatively low cost, simple design and high space‐charge capacity make it suitable for tackling complex scientific problems in which high performance is required. This review begins with a brief account of the set of inventions that led to the orbitrap, followed by a qualitative description of ion capture, ion motion in the trap and modes of detection. Various orbitrap instruments, including the commercially available linear ion trap–orbitrap hybrid mass spectrometers, are also discussed with emphasis on the different methods used to inject ions into the trap. Figures of merit such as resolving power, mass accuracy, dynamic range and sensitivity of each type of instrument are compared. In addition, experimental techniques that allow mass‐selective manipulation of the motion of confined ions and their potential application in tandem mass spectrometry in the orbitrap are described. Finally, some specific applications are reviewed to illustrate the performance and versatility of the orbitrap mass spectrometers. © 2008 Wiley Periodicals, Inc., Mass Spec Rev 27: 661–699, 2008

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Section: B Metabolomicsmentioning

confidence: 99%

Section: B Metabolomicsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Orbitrap mass spectrometry: Instrumentation, ion motion and applications

Perry

Cooks

Noll

2008

Mass Spectrometry Reviews

406

290

View full text Add to dashboard Cite

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“…These include acetylcholine esterase inhibitors [49], metabolites of the antidepressant/antiobesity drug Sibutramine™ [50], efaproxiral [51] and stanozolol [52]. Another group has recently reported a screening method allowing detection of 29 banned compounds, including drugs with antiestrogenic activity, b 2 -agonists, exogenous anabolic steroids and other anabolic agents.…”

Section: Applications N Drug Metabolismmentioning

confidence: 98%

Advances in Bioanalytical LC–MS Using the Orbitrap™ Mass Analyzer

Ščigelová

Makarov

2009

Bioanalysis

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The continuing desire to analyze complex biological samples with the minimum number of steps places high demands on increasing speed, dynamic signal range, quantitative capability and the facility with which the mass spectrometers can interface with chromatographic separation methods. Reliable identification of metabolites in complex mixtures requires robust mass spectrometers with high resolving power, mass accuracy, sensitivity and dynamic range, while tandem MS is an invaluable tool for further structural characterization. This review begins with a discussion of the key properties of the Orbitrap™ mass analyzer: mass accuracy, resolution, fidelity of isotope pattern abundancies and dynamic range. The main objective is to provide an overview of Orbitrap applications in the field of bioanalysis. Specific areas of drug metabolism, doping control and food contaminants are discussed in detail illustrating the performance and versatility of the Orbitrap mass analyzer.

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“…There have been a few reports that describe methods for the detection of efaproxiral in human urine samples for doping control purposes . Two of those assays enabled the determination of efaproxiral in human urine using gas chromatography‐mass spectrometry (GC‐MS) .…”

Section: Introductionmentioning

confidence: 99%

Detection of efaproxiral (RSR13) and its metabolites in equine by liquid chromatography tandem mass spectrometry

et al. 2014

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Efaproxiral (RSR 13) is an experimental synthetic allosteric modifier of haemoglobin (Hb) that acts by increasing the release of oxygen from Hb to the surrounding tissues. It has been shown to increase maximum oxygen uptake (VO(2max)) in a canine skeletal muscle model. The ability to increase maximal muscle oxygen uptake makes efaproxiral a potential performance-enhancing agent and is therefore prohibited by the World Anti-Doping Agency. In this study, a method for the detection and elimination of efaproxiral in equine plasma and urine after a 2.5 g intravenous administration of efaproxiral is described. Post administration plasma and urine samples were collected up to 120 h. Efaproxiral was detected up to 120 h in urine and up to 78 h in plasma. In plasma, the peak concentration was 42 µg/ml and detected at 5 min post administration. In urine, the peak concentration was 2.8 mg/ml and detected at 0-1 h post administration. A validated liquid chromatography tandem mass spectrometry method was used for the quantitation of efaproxiral in equine plasma and urine. The limit of detection of the method is 0.05 ng/ml in plasma and 0.1 ng/ml in urine. The method is highly sensitive and specific with good precision, accuracy and recovery. The manuscript also describes the systematic identification of efaproxiral metabolites detected in post administration equine urine samples. The metabolites were identified by use of enhanced mass spectra and enhanced product ion scans. Both positive and negative mode ionizations were utilized for metabolite identification and plausible fragmentation pathways were proposed for the phase 1 metabolite identified. In addition to free efaproxiral, one phase 1 metabolite and two phase 2 metabolites were identified in post administration urine.

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Mass spectrometric characterization of efaproxiral (RSR13) and its implementation into doping controls using liquid chromatography–atmospheric pressure ionization‐tandem mass spectrometry

Cited by 17 publications

References 16 publications

Orbitrap mass spectrometry: Instrumentation, ion motion and applications

Orbitrap mass spectrometry: Instrumentation, ion motion and applications

Advances in Bioanalytical LC–MS Using the Orbitrap™ Mass Analyzer

Detection of efaproxiral (RSR13) and its metabolites in equine by liquid chromatography tandem mass spectrometry

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