State of the art: Sphingomyelin (SPH) is a type of sphingolipid found in animal nerve tissues, especially in the membranous myelin sheath that surrounds some nerve cell axons. Because of its characteristics, SPH stationary phase represents an ideal tool to mimic the interactions taking place between active pharmaceutical ingredients and neurons. Method: The IAM.SPH stationary phase (0.821 mg) 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 μL min−1 at 25°C using a mobile phase consisting of 60/25/15 (v/v/v) Dulbecco's phosphate buffer saline pH 7.4/methanol/acetonitrile. The elution was achieved isocratically and monitored by UV detection at 220 nm. The investigated dataset consisted of 88 compounds (36 neutrals, 26 bases and 26 acids). The block relevance (BR) analysis was accomplished starting by calculating 82 descriptors using the software VS+ and submitting the data matrices to Matlab. Multiple linear regression and related descriptors were obtained with Vega ZZ 64. Results and discussion: The method developed allowed to achieve a solid and reproducible SPH affinity scale for the assayed compounds. Computational studies produced statistically significant models for the prediction and mechanism elucidation of the retentive behavior of pharmaceutically relevant compounds on the SPH stationary phase. Conclusions: For ionizable compounds, the IAM.SPH exhibited an original selectivity when compared to the commercially available IAM.PC. Moreover, apart from its suitability to surrogate log BB, IAM.SPH was also found relate significantly with the drugs’ fraction unbound in plasma, a crucial parameter in pharmacokinetics.

Into the first biomimetic sphingomyelin stationary phase: Suitability in drugs’ biopharmaceutic profiling and block relevance analysis of selectivity

Ermondi G.;Caron G.;
2021-01-01

Abstract

State of the art: Sphingomyelin (SPH) is a type of sphingolipid found in animal nerve tissues, especially in the membranous myelin sheath that surrounds some nerve cell axons. Because of its characteristics, SPH stationary phase represents an ideal tool to mimic the interactions taking place between active pharmaceutical ingredients and neurons. Method: The IAM.SPH stationary phase (0.821 mg) 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 μL min−1 at 25°C using a mobile phase consisting of 60/25/15 (v/v/v) Dulbecco's phosphate buffer saline pH 7.4/methanol/acetonitrile. The elution was achieved isocratically and monitored by UV detection at 220 nm. The investigated dataset consisted of 88 compounds (36 neutrals, 26 bases and 26 acids). The block relevance (BR) analysis was accomplished starting by calculating 82 descriptors using the software VS+ and submitting the data matrices to Matlab. Multiple linear regression and related descriptors were obtained with Vega ZZ 64. Results and discussion: The method developed allowed to achieve a solid and reproducible SPH affinity scale for the assayed compounds. Computational studies produced statistically significant models for the prediction and mechanism elucidation of the retentive behavior of pharmaceutically relevant compounds on the SPH stationary phase. Conclusions: For ionizable compounds, the IAM.SPH exhibited an original selectivity when compared to the commercially available IAM.PC. Moreover, apart from its suitability to surrogate log BB, IAM.SPH was also found relate significantly with the drugs’ fraction unbound in plasma, a crucial parameter in pharmacokinetics.
2021
156
105585
105600
biomimetic liquid chromatography; block relevance analysis; blood-brain barrier; immobilized artificial membrane; retention time prediction; sphingomyelin
Russo G.; Ermondi G.; Caron G.; Verzele D.; Lynen F.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/1765637
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