Chemical derivatization to enhance ionization of anabolic steroids in LC-MS for doping-control analysis

Abstract Anabolic androgenic steroids are the most frequently misused compounds in human sports, despite their prohibition by the International Olympic Committee and the World Anti-Doping Agency. In equestrian sports, this class of substances has also been prohibited by the national equestrian federations and the Federation Equestre Internationale. It is well known that the applicability of liquid chromatography-mass spectrometry (LC-MS) in the detection of these substances presents sensitivity limitations. The absence of acidic or basic groups or conjugated oxo-systems in the structures of some anabolic steroids explains their ionization difficulties in soft atmospheric pressure ionization (API) sources [e.g., electrospray ionization (ESI), atmospheric pressure chemical ionization or atmospheric pressure photoionization]. The goal of chemical derivatization is conversion of a poorly ionizable or non-ionizable compound into an easily detectable one by changing its chemical and physical properties and it is considered as a useful strategy for the ionization enhancement of anabolic steroids in API-MS techniques. This review underlines the efforts made in the human and animal doping-control fields to develop and to apply derivatization methods for enhancing ESI efficiency of banned anabolic steroids, so improving their detection in LC-MS analysis according to their established minimum required performance limits.