Systematic examination of supplement products available in the market in order to target and substance standard development

Code: 17A21CG 

It has been found that a number of supplements available internationally via the internet contain banned substances which are not specifically listed on the World Anti-Doping Agency (WADA) Prohibited List. These new compounds are generally termed ‘designer durgs’. Even though they are not specifically named in the WADA Prohibited List, the List allows for inclusion of new substances with similar structure or biological actions to drugs already on the
List. However this presumes that the substance can be detected by the normal drug screening procedures. To achieve the sensitivity required in screening methods they need to target specific compounds and this information is gained by studying the metabolism of the substances in the body. Every time a new substance is introduced a detection ‘gap’ is present until the substance’s metabolism has been studied extensively.

Currently there are many such compounds to be investigated. The aim of this project is to obtain supplements currently sold on the internet, establish the identity of the main ingredients and study the metabolism of a select number of these substances and determine procedures to allow them to be introduced into current testing schemes across all WADA-accredited laboratories.

Main Findings: 

The use of performance and image enhancing drugs (PIEDs) in the community is increasing. The types of drugs are moving from the traditional anabolic-androgenic steroids of the past, increasingly toward selective androgen receptor modulators (SARMs) and metabolic modulators. Most PIEDs have yet to complete clinical trials, so their toxicity and drug-drug interactions are unknown. Due to limited regulatory interest, these PIEDs are easily accessible online and often sold alongside sports supplements. Studies on products containing these PIEDs are also limited, and there is a lack of knowledge about their quality and availability. 
A survey of 107 oral liquid products purporting to contain PIEDs were purchased from Australian online retailers. A further 4 PIEDs were obtained from a seizure. The websites of the suppliers and the products themselves were appraised to gather intelligence on the marketing and presentation of these products. The PIEDs products themselves were analysed by liquid chromatography-high resolution quadrupole mass spectrometry (LC-qHRMS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) to assess the contamination, concentration, and homogeneity of the PIED products. 
It was found that most PIED products contained drugs, were highly contaminated, and were of poor quality. The SARMs were generally better quality than the other PIEDs classes assessed, and quality issues were generally consistent across suppliers. Additionally, the compound AC-262,536 was found to be in two of the products, meaning it is accessible in the market. In vitro metabolism studies using human liver microsomes (HLM) and S9 liver fraction were conducted, revealing that hydroxylation and glucuronidation of the parent and hydroxylated compound were the main metabolites.