Isotope ratio mass spectrometry - history and terminology in brief.

The history of isotope ratio mass spectrometry (IRMS) is briefly described. It is shown that the fundamental design of isotope ratio mass spectrometers has not changed since the 1940s. The basic findings concerning the natural variation of isotope abundances even date back to the 1930s. Recent improvements in the methodology mainly concern online coupling and analytical peripherals. The nature of isotopic scales necessitates a specific terminology which is unfamiliar to many analysts. However, corresponding guidelines exist that should be adopted by the anti-doping community. Currently, steroids represent the only group of compounds routinely analyzed by IRMS in doping-control. Suggestions are made in respect to a harmonized terminology concerning the nature and origins of steroids.

Classification of two steroids, prostanozol and methasterone, as Schedule III anabolic steroids under the Controlled Substance Act. Final rule.

With the issuance of this Final Rule, the Administrator of the DEA classifies the following two steroids as "anabolic steroids'' under the Controlled Substances Act (CSA): prostanozol (17[beta]-hydroxy-5[alpha]-androstano[3,2-c]pyrazole) and methasterone (2[alpha],17[alpha]-dimethyl-5[alpha]-androstan-17[beta]-ol-3-one). These steroids and their salts, esters, and ethers are Schedule III controlled substances subject to the regulatory control provisions of the CSA.

Classification of three steroids as schedule III anabolic steroids under the Controlled Substances Act. Final rule.

With the issuance of this final rule, the Deputy Administrator of the Drug Enforcement Administration (DEA) classifies the following three steroids as "anabolic steroids" under the Controlled Substances Act (CSA): Boldione, desoxymethyltestosterone, and 19-nor-4,9(10)-androstadienedione. These steroids and their salts, esters, and ethers are schedule III controlled substances subject to the regulatory control provisions of the CSA.

Applying pattern recognition methods plus quantum and physico-chemical molecular descriptors to analyze the anabolic activity of structurally diverse steroids.

The great cost associated with the development of new anabolic-androgenic steroid (AASs) makes necessary the development of computational methods that shorten the drug discovery pipeline. Toward this end, quantum, and physicochemical molecular descriptors, plus linear discriminant analysis (LDA) were used to analyze the anabolic/androgenic activity of structurally diverse steroids and to discover novel AASs, as well as also to give a structural interpretation of their anabolic-androgenic ratio (AAR). The obtained models are able to correctly classify 91.67% (86.27%) of the AASs in the training (test) sets, respectively. The results of predictions on the 10% full-out cross-validation test also evidence the robustness of the obtained model. Moreover, these classification functions are applied to an "in house" library of chemicals, to find novel AASs. Two new AASs are synthesized and tested for in vivo activity. Although both AASs are less active than some commercially AASs, this result leaves a door open to a virtual variational study of the structure of the two compounds, to improve their biological activity. The LDA-assisted QSAR models presented here, could significantly reduce the number of synthesized and tested AASs, as well as could increase the chance of finding new chemical entities with higher AAR.

[Ongoing medical problems in the anti-doping fight]. / Problèmes médicaux actuels de la lutte antidopage.

Over the last 20 years systematic doping has become a major threat for elite sport. So far, there is no clear information about the daily practice of doping. Repeated scandals and recent personal statements have added to our knowledge. Several more recent doping agents like Erythropoietin (EPO) and, probably, growth hormone (GH) enhance performance in a highly effective way and, together with the well known anabolic steroids (AAS), belong to the major doping categories. The introduction of EPO has really changed the paradigm in endurance sports allowing a good middle class athlete to become a champion. It is evident that doping practices are influenced by the possibilities of the anti-doping control system. Unethical, criminal medical doctors play a decisive role in the ongoing practice of major doping. Apart from the already mentioned substances AAS, EPO and GH several novel drugs appear on the horizon. They are highly effective and there is no doubt that they will be used in attempts to improve performance. During the last years, doping control systems have also been improved: EPO can now be detected in urine samples and the detection of AAS has also become much more sensitive. However GH hormone detection is not possible at the moment and this remains a major weakness of doping control. Other problems are the control procedures which are far from being optimal. In the future the quality of doping controls will be decisive and not only the quantity; controls will have to be "intelligent". The effective fight against doping in the next years will decide about the survival of elite sport.

Classification of anabolic steroids using the method of competitive metabolism.

The effect of increasing concentrations of testosterone (T) and 19-nortestosterone (N) on the in vitro metabolism of [3H]N in minced tissue of the rat seminal vesicle indicates that T and N are equally appropriate substrates for the 5 alpha-reductase. Experiments in which increasing concentrations of 17-methyl-T (MT) or 1-ene-MT were incubated with [3H]T and vesicular mince have revealed that the formation of [3H]5 alpha-dihydro-T is suppressed markedly by MT while 1-ene-MT has no measurable effect. Since 5 alpha-dihydro-MT binds to the androgen receptor with a higher affinity than MT does and (relative to T) MT does not exhibit myotropic-androgenic (= M-A) dissociation, it can be concluded that MT is, whereas 1-ene-MT is not a substrate for the 5 alpha-reductase. Our present and previous data suggest that N exemplifies one class of anabolic steroids that become less androgenic due to 5 alpha-reduction, it shows high myotropic activity, M-A dissociation (= 7-30) and affinity to the androgen receptor. On the other hand, 1-ene-MT belongs to another class of anabolic steroids that are not substrates for the 5 alpha-reductase, exhibit a relatively small myotropic activity, M-A dissociation (= 2-3) and receptor affinity.