ADMET and DMPK, Vol. 8 No. 1, 2020.
Original scientific paper
https://doi.org/10.5599/admet.757
Revisiting the application of Immobilized Artificial Membrane (IAM) chromatography to estimate in vivo distribution properties of drug discovery compounds based on the model of marketed drugs
Klara Valko
; Bio-Mimetic Chromatography Ltd. Business and Technology Centre, Bessemer Drive, Stevenage, SG1 2DX, United Kingdom
Silvia Rava
; University of Pavia, Italy, Erasmus internship at Bio-Mimetic Chromatography Ltd. Business and Technology Centre, Bessemer Drive, Stevenage, SG1 2DX, United Kingdom
Shenaz Bunally
; Physicochemical Group, GSK, Gunnels Wood Road, Stevenage, SG1 2NY United Kingdom
Scott Anderson
; Regis Technologies Inc. 8210 Austin Avenue Morton Grove, IL US 60053
Abstract
Immobilized Artificial Membrane (IAM) chromatography columns have been used to model the in vivo distribution of drug discovery compounds. Regis Technologies Inc., the manufacturer, had to replace the silica support and consequently introduced a new IAM.PC.DD2 column that shows slightly different selectivity towards acidic and basic compounds. The application of the new IAM.PC.DD2 columns has been evaluated and the in vivo distribution models have been compared with the previous batches of columns. It was found that due to the improved endcapping of the silica, some of the positively charged drug molecules showed shorter retention than previously published. Therefore, the column system suitability data have been updated. However, these differences do not significantly affect the previously published models for the volume of distribution, brain tissue binding and drug efficiency. Therefore, the published models can be used with the new IAM.PC.DD2 columns.
Keywords
Phospholipid binding; HPLC; volume of distribution; tissue binding,; drug efficiency
Hrčak ID:
235013
URI
Publication date:
4.3.2020.
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