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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

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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 (r(2) (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.
Keywords
HUMAN INTESTINAL-ABSORPTION, PARTITION-COEFFICIENTS, POLAR INTERACTIONS, IAM-HPLC, DRUG RESEARCH, PENETRATION, DESCRIPTORS, PERMEATION, PREDICTION, CHEMISTRY, Immobilized artificial membrane, Time-of-flight mass spectrometry, Blood-brain barrier, Quantitative structure-activity relationship, Liquid chromatography, High-throughput

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Citation

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MLA
Russo, Giacomo et al. “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.” EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS 127 (2018): 72–84. Print.
APA
Russo, Giacomo, Grumetto, L., Szucs, R., Barbato, F., & Lynen, F. (2018). 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. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, 127, 72–84.
Chicago author-date
Russo, Giacomo, Lucia Grumetto, Roman Szucs, Francesco Barbato, and Frederic Lynen. 2018. “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.” European Journal of Pharmaceutics and Biopharmaceutics 127: 72–84.
Chicago author-date (all authors)
Russo, Giacomo, Lucia Grumetto, Roman Szucs, Francesco Barbato, and Frederic Lynen. 2018. “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.” European Journal of Pharmaceutics and Biopharmaceutics 127: 72–84.
Vancouver
1.
Russo G, Grumetto L, Szucs R, Barbato F, Lynen F. 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. EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS. 2018;127:72–84.
IEEE
[1]
G. Russo, L. Grumetto, R. Szucs, F. Barbato, and F. Lynen, “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,” EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS, vol. 127, pp. 72–84, 2018.
@article{8599669,
  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 (r(2) (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.},
  author       = {Russo, Giacomo and Grumetto, Lucia and Szucs, Roman and Barbato, Francesco and Lynen, Frederic},
  issn         = {0939-6411},
  journal      = {EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS},
  keywords     = {HUMAN INTESTINAL-ABSORPTION,PARTITION-COEFFICIENTS,POLAR INTERACTIONS,IAM-HPLC,DRUG RESEARCH,PENETRATION,DESCRIPTORS,PERMEATION,PREDICTION,CHEMISTRY,Immobilized artificial membrane,Time-of-flight mass spectrometry,Blood-brain barrier,Quantitative structure-activity relationship,Liquid chromatography,High-throughput},
  language     = {eng},
  pages        = {72--84},
  title        = {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},
  url          = {http://dx.doi.org/10.1016/j.ejpb.2018.02.004},
  volume       = {127},
  year         = {2018},
}

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