Unraveling the molecular interactions driving retention and selectivity of a sphingomyelin-based stationary phase by QSPR interpreted through block relevance analysis

State of the art: Sphingomyelin (SPH) is a type of sphingolipid found in animal cell membranes in a range from 2 to 15% mol/mol in most tissues. However, SPH features higher concentrations in red blood cells, the ocular lenses and nerve tissues, especially in the membranous myelin sheath that surrounds some nerve cell axons. As a consequence of its characteristics, SPH stationary phase represents an ideal tool to mimic the interactions taking place between active pharmaceutical ingredients and neurons. Method: The SPH stationary phase (0.821 mg), synthesized by the Separation Science Group in 2012(1), was suspended in methanol (7.0 mL) and the resulting slurry packed (600 bar) in an HPLC column (10 cm x 2.1 mm). The column was operated at 300 mL/min at 25 °C using a mobile phase consisting of 60/25/15 Dulbecco’s phosphate buffer saline pH 7.4/methanol/acetonitrile. The elution was achieved isocratically and monitored by UV detection at 220 nm. The databased assayed consisted of 36 neutral compounds, 26 basic molecules and 26 acids. Results: QSPR study allowed accurate prediction and mechanism elucidation of the retentive behavior of pharmaceutically relevant compounds on the SPH stationary phase. Moreover, block relevance analysis assisted in rationalizing the intermolecular driving forces involved in the chromatographic retention. References: [1] Verzele, D.; Lynen, F.; De Vrieze, M.; Wright, A. G.; Hanna-Brown, M.; Sandra, P., Development of the first sphingomyelin biomimetic stationary phase for immobilized artificial membrane (IAM) chromatography. Chem Commun (Camb) 2012, 48 (8), 1162-4