Separating closely resembling steroids with ionic liquids in liquid–liquid extraction systems

• Pregnenolone and progesterone were separated by liquid–liquid extraction with ILs.
• BMIM BF4 was selected with tert-butyl methyl ether (TBME) as solvent system.
• Up to 10 mM, competitive partitioning isotherms were linear.
• BMIM BF4 in silica solvent immobilization studied experimentally. High purity, limited yield.
• Multistage fractional extraction studied by simulation, high purity possible with high yield.

Separation of steroids by liquid–liquid extraction with ionic liquids (ILs) as solvent was studied both experimentally and by simulation using a model mixture of progesterone and pregnenolone. The studies involved a solvent screening using COSMO-RS software for estimation of progesterone solubility. An experimental compatibility study of several solvents with reasonable progesterone solubility with several ILs. The results showed tert-butyl methyl ether (TBME)–butyl methyl imidazolium tetrafluoroborate (BMIM BF4) as the most promising solvent combination. Next, equilibrium partitioning of both progesterone and pregnenolone in this solvent combination was determined experimentally. Fixed bed studies using solvent impregnated resin (SIR) obtained by impregnation of BMIM BF4 in silica showed that it is feasible to obtain highly pure progesterone in such a process. However, the yield was far from quantitative and thus a fractional extraction process was studied by simulation of a counter current extraction process. The simulation study showed that with fractional extraction highly pure progesterone (excess >0.99) can be obtained at a yield of >0.95 when a minimum of 24 equilibrium stages are applied.