Research on the Application of Isotope Ratio Mass Spectrometry Technology in Traceability Detection of Stimulants

DOI: https://doi.org/10.62517/jes.202402114

Author(s)

Yue Zhuo#, Yirang Wang#, Xiaomeng Xiang#, Bing Liu*

Affiliation(s)

Shanghai University of sport, Jiangwancheng Road 900, Shanghai, P. R. China *Corresponding Author. #These authors contributed equally to the research.

Abstract

Endogenous substances, which are produced by the body itself, have become a focus of concern due to their potential abuse as stimulants in sports. The chemical structure and physicochemical properties of externally synthesized endogenous substances are similar to those produced internally, making them difficult to detect. In response to this challenge, it is crucial to develop effective methods for detecting both endogenous and exogenous substances. One promising approach leverages the differences in stable carbon isotope abundance between internal and external sources, leading to changes in the Compound-Specific Isotope Ratio (CIR) after ingestion. The GC-C-IRMS method has emerged as a commonly used and highly accurate technique for tracing the origin of substances. Recognizing its significance in the fight against doping, the World Anti-Doping Agency (WADA) has standardized this method and established relevant benchmarks. This review article examines the advancements made over the past decade in detecting S1 anabolic steroids, S4 hormones and metabolic modulators, and S9 glucocorticoids. By offering a comprehensive overview of progress in the detection of endogenous substances using isotope ratio mass spectrometry, the aim is to provide valuable insights for enhancing existing anti-doping measures. This research serves as a critical reference point for ongoing efforts to combat the misuse of endogenous substances in the realm of sports.

Keywords

Endogenous Substance; Detection Method; Isotope Ratio Mass Spectrometry; Tracing the Origin of Doping

References

[1]Araghiniknam M, Chung S, Nelson-White T, et al. Antioxidant activity of dioscorea and dehydroepiandrosterone (DHEA) in older humans. Life Sciences, 1996, 59(11): PL147–PL157. [2]Winter K, Holtum J A M, Smith J A C. Crassulacean acid metabolism: a continuous or discrete trait? New Phytologist, 2015, 208(1): 73–78. [3]Winter K. Ecophysiology of constitutive and facultative CAM photosynthesis. Cushman. Journal of Experimental Botany, 2019, 70(22): 6495–6508. [4]Muccio Z, Jackson G P. Isotope ratio mass spectrometry. The Analyst, 2009, 134(2): 213–222. [5]Bartelink E J, Chesson L A. Recent applications of isotope analysis to for ensic anthropology. Forensic Sciences Research, 2019, 4(1): 29–44. [6]Gat J R. Oxygen and hydrogen isotopes in the hydrologic cycle. Annual Review of Earth and Planetary Sciences, 1996, 24(1): 225–262. [7]Seminoff J A, Benson S R, Arthur K E, et al. Stable Isotope Tracking of Endangered Sea Turtles: Validation with Satellite Telemetry and δ15N Analysis of Amino Acids. R. Reina. PLoS ONE, 2012, 7(5): e37403. [8]Shin W-J, Lee S-W, Heo S-Y, et al. Stable Isotopic Fingerprinting for Identification of the Methyl Tert-Butyl Ether (MTBE) Manufacturer. Environmental Forensics, 2013, 14(1): 36–41. [9]Kim H, Lee D-H, Go A, et al. Differentiation of endogenous and exogenous γ-Hydroxybutyrate in rat and human urine by GC/C/IRMS. International Journal of Legal Medicine, 2019, 133(6): 1785–1794. [10]Strojnik L, Potočnik D, Jagodic Hudobivnik M, et al. Geographical identification of strawberries based on stable isotope ratio and multi-elemental analysis coupled with multivariate statistical analysis: A Slovenian case study. Food Chemistry, 2022, 381: 132204. [11]Nehlich O, Barrett J H, Richards M P. Spatial variability in sulphur isotope values of archaeological and modern cod (Gadus morhua): Sulphur isotopes of cod. Rapid Communications in Mass Spectrometry, 2013, 27(20): 2255–2262. [12]Colonese A C, Farrell T, Lucquin A, et al. Archaeological bone lipids as palaeodietary markers: Lipids as dietary markers. Rapid Communications in Mass Spectrometry, 2015, 29(7): 611–618. [13]Oras E, Vahur S, Isaksson S, et al. MALDI-FT-ICR-MS for archaeological lipid residue analysis. Journal of Mass Spectrometry, 2017, 52(10): 689–700. [14]Benagiano M, Bianchi P, D’Elios M M, et al. Autoimmune diseases: Role of steroid hormones. Best Practice & Research Clinical Obstetrics & Gynaecology, 2019, 60: 24–34. [15]Zubeldia‐Brenner L, Roselli C E, Recabarren S E, et al. Developmental and Functional Effects of Steroid Hormones on the Neuroendocrine Axis and Spinal Cord. Journal of Neuroendocrinology, 2016, 28(7): jne.12401. [16]Mehta A, Nadkarni N, Patil S, et al. Topical corticosteroids in dermatology. Indian Journal of Dermatology, Venereology, and Leprology, 2016, 82(4): 371. [17]Geyer J, Bakhaus K, Bernhardt R, et al. The role of sulfated steroid hormones in reproductive processes. The Journal of Steroid Biochemistry and Molecular Biology, 2017, 172: 207–221. [18]Mędraś M, Brona A, Jóźków P. The Central Effects of Androgenic-anabolic Steroid Use. Journal of Addiction Medicine, 2018, 12(3): 184–192. [19]Albano G D, Amico F, Cocimano G, et al. Adverse Effects of Anabolic-Androgenic Steroids: A Literature Review. Healthcare, 2021, 9(1): 97. [20]Smit D L, de Hon O, Venhuis B J, et al. Baseline characteristics of the HAARLEM study: 100 male amateur athletes using anabolic androgenic steroids.:9. [21]World Anti-Doping Agency (WADA). TD2021APMU. 2020. [22]Forsdahl G, Vatne H K, Geisendorfer T, et al. Screening of testosterone esters in human plasma: Screening of testosterone esters. Drug Testing and Analysis, 2013, 5(11–12): 826–833. [23]Kintz P, Gheddar L, Raul J. Testing for anabolic steroids in human nail clippings. Journal of Forensic Sciences, 2021, 66(4): 1577–1582. [24]Yang M, Chen J, Wei W. Dimerization of glucocorticoid receptors and its role in inflammation and immune responses. Pharmacological Research, 2021, 166: 105334. [25]Mezzullo M, Fanelli F, Fazzini A, et al. Validation of an LC–MS/MS salivary assay for glucocorticoid status assessment: Evaluation of the diurnal fluctuation of cortisol and cortisone and of their association within and between serum and saliva. The Journal of Steroid Biochemistry and Molecular Biology, 2016, 163: 103–112. [26]Yan Y, Ai L, Zhang H, et al. Development an automated and high-throughput analytical platform for screening 39 glucocorticoids in animal-derived food for doping control. Microchemical Journal, 2021, 165: 106142. [27]Onizuka Y, Nagai K, Ideno Y, et al. Association between FSH, E1, and E2levels in urine and serum in premenopausal and postmenopausal women. Clinical Biochemistry, 2019, 73: 105–108. [28]Rodríguez C, Muñoz M, Contreras C, et al. AMPK, metabolism, and vascular function. The FEBS Journal, 2021, 288(12): 3746–3771. [29]Chen M-M, Li Y, Deng S-L, et al. Mitochondrial Function and Reactive Oxygen/Nitrogen Species in Skeletal Muscle. Frontiers in Cell and Developmental Biology, 2022, 10: 826981. [30]Thomas A, Vogel M, Piper T, et al. Quantification of AICAR-ribotide concentrations in red blood cells by means of LC-MS/MS. Analytical and Bioanalytical Chemistry, 2013, 405(30): 9703–9709. [31]Piper T, Thomas A, Baume N, et al. Determination of 13C/12C ratios of endogenous urinary 5-amino-imidazole-4-carboxamide 1β-D-ribofuranoside (AICAR): Determination of 13C/12C ratios of endogenous urinary AICAR. Rapid Communications in Mass Spectrometry, 2014, 28(11): 1194–1202. [32]Dmitrieva E V, Temerdashev A Z, Azaryan A A, et al. Application of Solid-Phase Extraction for the Quantification of Urinary AICAR by Ultra-High Performance Liquid Chromatography–Tandem Mass-Spectrometry. Journal of Analytical Chemistry, 2019, 74(9): 861–864. [33]Iannella L, Colamonici C, Curcio D, et al. 5α‐reductase inhibitors: Evaluation of their potential confounding effect on GC‐C‐IRMS doping analysis. Drug Testing and Analysis, 2021, 13(11–12): 1852–1861.