A very typical case of severe cholestasis due to anabolic steroid use. Because the steroids were being used without medical supervision, the dose and actual duration of use of each preparation was unclear, but cholestasis usually arises within 4 to 12 weeks of starting a C-17 alkylated androgenic steroid. The jaundice can be severe and prolonged and accompanied by severe pruritus and marked weight loss. The serum enzymes are typically minimally elevated except for a short period immediately after stopping therapy. The pattern of enzyme elevations can be hepatocellular, cholestatic or mixed. Liver biopsy shows a “bland” cholestasis with minimal inflammation and hepatocellular necrosis. Ma Huang has also been implicated in cases of drug induced liver injury, but is associated with an acute hepatocellular pattern of injury.
Detailed structural information on metabolites serving as target analytes in clinical, forensic, and sports drug testing programmes is of paramount importance to ensure unequivocal test results. In the present study, the utility of collision cross section (CCS) analysis by travelling wave ion mobility measurements to support drug metabolite characterization efforts was tested concerning recently identified glucuronic acid conjugates of the anabolic-androgenic steroid stanozolol. Employing travelling-wave ion mobility spectrometry/quadrupole-time-of-flight mass spectrometry, drift times of five synthetically derived and fully characterized steroid glucuronides were measured and subsequently correlated to respective CCSs as obtained in silico to form an analyte-tailored calibration curve. The CCSs were calculated by equilibrium structure minimization (density functional theory) using the programmes ORCA with the data set B3LYP/6-31G and MOBCAL utilizing the trajectory method (TM) with nitrogen as drift gas. Under identical experimental conditions, synthesized and/or urinary stanozolol-N and O-glucuronides were analyzed to provide complementary information on the location of glucuronidation. Finally, the obtained data were compared to CCS results generated by the system's internal algorithm based on a calibration employing a polyalanine analyte mixture. The CCSs ΩN2 calculated for the five steroid glucuronide calibrants were found between 180 and 208 Å(2) , thus largely covering the observed and computed CCSs for stanozolol-N1'-, stanozolol-N2'-, and stanozolol-O-glucuronide found at values between and Å(2) . The obtained data corroborated the earlier suggested N- and O-glucuronidation of stanozolol, and demonstrate the exploit of ion mobility and CCS computation in structure characterization of phase-II metabolic products; however, despite reproducibly measurable differences in ion mobility of stanozolol-N1'-, N2'-, and O-glucuronides, the discriminatory power of the chosen CCS computation algorithm was found to be not appropriate to allow for accurate assignments of the two N-conjugated structures. Using polyalanine-based calibrations, significantly different absolute values were obtained for all CCSs, but due to a constant offset of approximately 45 Å(2) an excellent correlation (R(2) = ) between both approaches was observed. This suggests a substantially accelerated protocol when patterns of computed and polyalanine-based experimental data can be used for structure elucidations instead of creating individual analyte-specific calibration curves.
Typically, any athlete who tests positive for banned substances after having served a previous ban receives a lifetime ban from the sport of athletics. Many high-profile sportspeople to receive doping bans have come from the sport of athletics, with significant past cases concerning Ben Johnson , Marion Jones and Tim Montgomery . Furthermore, a number of athletes who underwent state-sponsored doping programmes in East Germany between the 1960s and 1980s were competitors in athletics, but the quality of the international anti-doping work was so poor that only one East German athlete ever tested positive.  Following allegations of state-sponsored doping in Russia , the IAAF suspended the country's athletes from competition, including the 2016 Summer Olympics.