AN INVESTIGATION INTO POLYDRUG USE IN COMBINATION WITH ANABOLIC-ANDROGENIC STEROIDS

Abstract

Background: The use of anabolic-androgenic steroids (AASs), a class of image and performance enhancing drugs (IPEDs), is growing in prevalence, with known adverse health effects associated with long-term use providing means for concern. In addition, relatively high polydrug use is observed within the AAS administering population. A desire for greater research into AAS polydrug use is a consistent theme throughout previously published literature as very little is known about the health concerns and the practices relating to AAS polydrug use.

Methods: An online questionnaire (n=202) was conducted to investigate AAS use, demographic trends, and polydrug administration. Statistical analyses (Chi-square and Spearman’s rank correlation) were performed in SPSS. Using these results, and information from previously published literature. 22 AASs, AAS metabolites and associated IPEDs were selected for inclusion in the development of a gas chromatography–mass spectrometry (GC-MS) method. Extraction (LLE, SPE, QuEChERS), derivatisation (heat block vs. microwave-assisted derivatisation), and GC-MS parameters were optimised for analytical efficiency. Method validation followed ANSI/ASB 036 and WADA guidelines. Additionally, pooled human liver microsomes (HLMs) were used to examine the impact of AASs on the metabolic clearance of co-administered drugs (ADB-FUBIATA, CH-PIATA, quetiapine).

Results: Out of 202 respondents, 115 self-reported lifetime AAS use and 70 for less than one year; 76.8% were aged 18–34, and 57.4% reported co-administering other IPEDs or recreational substances. The GC-MS method successfully enabled the simultaneous detection of 18 AASs and metabolites, although was not able to be fully validated. The final run time was reduced from 27.5 to 19 minutes. Of seven blind forensic workplace samples analysed, the method produced full or partial identification in agreement with the forensic service provider in six samples, confirming its real-world applicability for the qualitative analysis of AASs.

In HLM incubations, AASs did not markedly alter the clearance of ADB-FUBIATA or quetiapine. However, CH-PIATA exhibited a ~3-fold reduction in intrinsic clearance when co-incubated with metandienone and a ~2-fold reduction with nandrolone and testosterone, suggesting potential drug-drug interactions (DDIs). For the first time the experimental HLM clearance of ADB-FUBIATA is reported.

Conclusion: This thesis provides a novel, qualitative GC-MS method for AAS detection. The findings highlight the prevalence and complexity of polydrug use among AAS users and demonstrate the feasibility of assessing DDIs via in vitro microsomal studies. However, the challenges experienced during the validation of the method to ASNI/ASB 036 standards highlight the difficulty in developing AAS methods for use outside specialist anti-doping laboratories.

Date of Award	2025
Original language	English
Awarding Institution	University of Dundee
Supervisor	Lorna Nisbet (Supervisor) & Sarah Hall (Supervisor)