Dr Giacomo Russo G.Russo@napier.ac.uk
Lecturer
Screening therapeutics according to their uptake across the blood-brain barrier: A high throughput method based on immobilized artificial membrane liquid chromatography-diode-array-detection coupled to electrospray-time-of-flight mass spectrometry
Russo, Giacomo; Grumetto, Lucia; Szucs, Roman; Barbato, Francesco; Lynen, Frederic
Authors
Lucia Grumetto
Roman Szucs
Francesco Barbato
Frederic Lynen
Abstract
The Blood-Brain Barrier (BBB) plays an essential role in protecting the brain tissues against possible injurious substances. In the present work, 79 neutral, basic, acidic and amphoteric structurally unrelated analytes were considered and their chromatographic retention coefficients on immobilized artificial membrane (IAM) stationary phase were determined employing a mass spectrometry (MS)-compatible buffer based on ammonium acetate. Their BBB passage predictive strength was evaluated and the statistical models based on IAM indexes and in silico physico-chemical descriptors showed solid statistics (r² (n − 1) = 0.78). The predictive strength of the indexes achieved by the MS-compatible method was comparable to that achieved by employing the more “biomimetic” Dulbecco’s phosphate buffered saline, even if some differences in the elution order were observed. The method was transferred to the MS, employing a diode-array-detection coupled to an electrospray ionization source and a time-of-flight analyzer. This setup allowed the simultaneous analysis of up to eight analytes, yielding a remarkable acceleration of the analysis time.
Journal Article Type | Article |
---|---|
Acceptance Date | Feb 5, 2018 |
Online Publication Date | Feb 7, 2018 |
Publication Date | 2018-06 |
Deposit Date | Mar 31, 2020 |
Journal | European Journal of Pharmaceutics and Biopharmaceutics |
Print ISSN | 0939-6411 |
Publisher | Elsevier |
Peer Reviewed | Peer Reviewed |
Volume | 127 |
Pages | 72-84 |
DOI | https://doi.org/10.1016/j.ejpb.2018.02.004 |
Keywords | Immobilized artificial membrane; Time-of-flight mass spectrometry; Blood-brain barrier; Quantitative structure-activity relationship; Liquid chromatography; High-throughput |
Public URL | http://researchrepository.napier.ac.uk/Output/2649483 |
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