GC/MS in Recent Years Has Defined the Normal and Clinically Disordered Steroidome: Will It Soon Be Surpassed by LC/Tandem MS in This Role?

Gas chromatography/mass spectrometry (GC/MS) has been used for steroid analysis since the 1960s. The advent of protective derivatization, capillary columns, and inexpensive electron ionization bench-top single quadrupole soon made it the method of choice for studying disorders of steroid synthesis and metabolism. However, the lengthy sample workup prevented GC/MS from becoming routine for steroid hormone measurement, which was dominated by radioimmunoassay. It was the emergence of liquid chromatography/tandem MS (LC/MS/MS) that sparked a renewed interest in GC/MS for the multicomponent analysis of steroids. GC/MS is excellent at providing an integrated picture of a person's steroid metabolome, or steroidome, as we term it. We review the recent work on newly described disorders and discuss the technical advances such as GC coupling to triple quadrupole and ion trap analyzers, two-dimensional GC/MS, and alternative ionization and detection systems such as atmospheric pressure chemical ionization (APCI) and time of flight. We believe that no novel GC/MS-based technique has the power of GC(electron ionization)/MS/MS as a “discovery tool,” although APCI might provide ultimate sensitivity, which might be required in tissue steroidomics. Finally, we discuss the role of LC/MS/MS in steroidomics. This remains a challenge but offers shorter analysis times and advantages in the detection and discovery of steroids with a known structure. We describe recent advances in LC/MS steroidomics of hydrolyzed and intact steroid conjugates and suggest the technique is catching up with GC/MS in this area. However, in the end, both techniques will likely remain complementary and both should be available in advanced analytical laboratories.