The application of carbon isotope ratio mass spectrometry to doping control

Abstract

The administration of synthetic steroid copies is one of the most important issues facing sports. Doping control laboratories accredited by the World Anti-Doping Agency (WADA) require methods of analysis that allow endogenous steroids to be distinguished from their synthetic analogs in urine. The ability to measure isotope distribution at natural abundance with high accuracy and precision has increased the application of Gas Chromatography-Combustion-Isotope Ratio Mass Spectrometry (GC-C-IRMS) to doping control in recent years. GC-C-IRMS is capable of measuring the carbon isotope ratio (d 13 KEYWORDS: endogenous steroids; doping control; carbon isotope ratio (υ 13 C); gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS) THE ENDOGENOUS STEROID CHALLENGEDrug use and abuse is an unfortunate feature of sports. The fight against doping in sports is a challenge faced by governments, sports authorities, laboratories, coaches and athletes who wish to contribute to fair, healthy and legal competition. The abuse of synthetic steroid copies is one of the most important issues for doping control. Before 1982, only the use of xenobiotic steroids had been banned, with a positive result requiring unequivocal proof provided by techniques such as GC-MS that the banned substance and/or its metabolites were present in a urine sample. Following the prohibition of testosterone (T; androst-4-ene-17ˇ-ol-3-one) administration by the International Olympic Committee and subsequently by the World Anti-Doping Agency (WADA), 1 new areas of research have been established within doping control laboratories.Methods for the detection of administered synthetic steroids by molecular spectrometry techniques such as GC-MS are limited by their ability to identify and quantify. The GC-MS steroid profiles are, however, an important Ł Correspondence to: Adam T. Cawley, National Measurement Institute, 1 Suakin Street, Pymble NSW 2073, Australia. E-mail: Adam.Cawley@measurement.gov.au means of screening all urine samples entering the laboratory to eliminate those of nonsuspicious nature. The objective for doping control laboratories is, therefore, to maximize the detection of synthetic steroid doping violations while minimizing the additional resources required from stakeholders. This can be achieved with advanced GC-MS steroid profiling strategies based on the analysis of several urinary steroids that can originate from the endocrine system. 2 -7 Control of any endogenous substance requires the establishment of 'normal' reference intervals and subsequent statistical determination of what constitutes an 'abnormal' state. The challenge for doping control is presented by steroid administration altering the human endocrine system in ways that are not yet fully understood, since they are largely dependent on the individual athlete.Synthetic copies of endogenous steroids, namely, dehydroepiandrosterone [(DHEA); androst-5-ene-3ˇ-ol-17-one], androstenedione (ADIONE; androst-4-ene-3,17-dione), 4-androstenediol (4-ADIOL; androst-4-ene-3ˇ,17...

Recent developments in the use of isotope ratio mass spectrometry in sports drug testing

“…Furthermore, IRMS values of steroid degradation products such as 5α-androstan-3,17-dione and 5β-androstan-3,17-dione were investigated, showing strong isotopic fractionation especially during the formation of DCM by deconjugation of DHEA_S [84]. Finally, two reviews on IRMS in doping analysis have been published [85,86].…”

Some aspects concerning modifications of the List of Prohibited Substances and Methods in sport

“…This method allows to detect the origin of the appearance of anabolic-androgenic steroids (endogenic or exogenic) in an organism [5]. Recently, the IRMS analysis becomes a standard procedure performed for all samples with the T/E ratio greater than 4.…”

Annual banned‐substance review: analytical approaches in human sports drug testing

“…[8] Despite the proven capability of IRMS instruments to accurately measure isotope ratios of hydrogen, nitrogen, or carbon, for example, the application of the technique to doping controls has been challenged in the past with regard to particular cases. [9] However, numerous studies outlining the enormous utility and reliability of established methods as well as continuous research allowing the extension and improvement of assays have further strengthened the position of GC/C/IRMS in doping controls.…”