A fully automated nanoelectrospray tandem mass spectrometric method for analysis of Caco-2 samples

Caco‐2 cells offer a means to rapidly screen permeability of drug candidates, allowing pharmaceutical companies to eliminate candidates unable to cross the intestinal barrier early in the discovery process. This screening process is typically performed by conventional liquid chromatography/tandem ma...

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Published inRapid communications in mass spectrometry Vol. 17; no. 14; pp. 1573 - 1578
Main Authors Van Pelt, Colleen K., Zhang, Sheng, Fung, Eliza, Chu, Inhou, Liu, Tongtong, Li, Cheng, Korfmacher, Walter A., Henion, Jack
Format Journal Article
LanguageEnglish
Published Chichester, UK John Wiley & Sons, Ltd 01.01.2003
Subjects
Online AccessGet full text
ISSN0951-4198
1097-0231
DOI10.1002/rcm.1087

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Abstract Caco‐2 cells offer a means to rapidly screen permeability of drug candidates, allowing pharmaceutical companies to eliminate candidates unable to cross the intestinal barrier early in the discovery process. This screening process is typically performed by conventional liquid chromatography/tandem mass spectrometry (LC/MS/MS), which can require time‐consuming method development. An alternative to LC/MS/MS, automated nanoelectrospray tandem mass spectrometry (nanoESI‐MS/MS), is introduced. This novel approach requires an off‐line ZipTip™ desalting step followed by automated nanoESI‐MS/MS, using the NanoMate™ 100 and ESI Chip™. In addition to reduced method development time, automated nanoESI‐MS/MS also offers no carry‐over between samples, low sample consumption, and ease‐of‐use as compared with conventional pulled‐capillary nanoelectrospray. Furthermore, the infusion system described has the potential to be high‐throughput. A comparison of Caco‐2 samples analyzed both by LC/MS/MS and by automated nanoESI‐MS/MS is presented. The permeability and recovery data of the two compounds analyzed in this study obtained from conventional LC/MS/MS and by automated nanoESI‐MS/MS were in excellent agreement. Copyright © 2003 John Wiley & Sons, Ltd.
AbstractList Caco‐2 cells offer a means to rapidly screen permeability of drug candidates, allowing pharmaceutical companies to eliminate candidates unable to cross the intestinal barrier early in the discovery process. This screening process is typically performed by conventional liquid chromatography/tandem mass spectrometry (LC/MS/MS), which can require time‐consuming method development. An alternative to LC/MS/MS, automated nanoelectrospray tandem mass spectrometry (nanoESI‐MS/MS), is introduced. This novel approach requires an off‐line ZipTip™ desalting step followed by automated nanoESI‐MS/MS, using the NanoMate™ 100 and ESI Chip™. In addition to reduced method development time, automated nanoESI‐MS/MS also offers no carry‐over between samples, low sample consumption, and ease‐of‐use as compared with conventional pulled‐capillary nanoelectrospray. Furthermore, the infusion system described has the potential to be high‐throughput. A comparison of Caco‐2 samples analyzed both by LC/MS/MS and by automated nanoESI‐MS/MS is presented. The permeability and recovery data of the two compounds analyzed in this study obtained from conventional LC/MS/MS and by automated nanoESI‐MS/MS were in excellent agreement. Copyright © 2003 John Wiley & Sons, Ltd.
Caco-2 cells offer a means to rapidly screen permeability of drug candidates, allowing pharmaceutical companies to eliminate candidates unable to cross the intestinal barrier early in the discovery process. This screening process is typically performed by conventional liquid chromatography/tandem mass spectrometry (LC/MS/MS), which can require time-consuming method development. An alternative to LC/MS/MS, automated nanoelectrospray tandem mass spectrometry (nanoESI-MS/MS), is introduced. This novel approach requires an off-line ZipTip desalting step followed by automated nanoESI-MS/MS, using the NanoMate 100 and ESI Chip. In addition to reduced method development time, automated nanoESI-MS/MS also offers no carry-over between samples, low sample consumption, and ease-of-use as compared with conventional pulled-capillary nanoelectrospray. Furthermore, the infusion system described has the potential to be high-throughput. A comparison of Caco-2 samples analyzed both by LC/MS/MS and by automated nanoESI-MS/MS is presented. The permeability and recovery data of the two compounds analyzed in this study obtained from conventional LC/MS/MS and by automated nanoESI-MS/MS were in excellent agreement.Caco-2 cells offer a means to rapidly screen permeability of drug candidates, allowing pharmaceutical companies to eliminate candidates unable to cross the intestinal barrier early in the discovery process. This screening process is typically performed by conventional liquid chromatography/tandem mass spectrometry (LC/MS/MS), which can require time-consuming method development. An alternative to LC/MS/MS, automated nanoelectrospray tandem mass spectrometry (nanoESI-MS/MS), is introduced. This novel approach requires an off-line ZipTip desalting step followed by automated nanoESI-MS/MS, using the NanoMate 100 and ESI Chip. In addition to reduced method development time, automated nanoESI-MS/MS also offers no carry-over between samples, low sample consumption, and ease-of-use as compared with conventional pulled-capillary nanoelectrospray. Furthermore, the infusion system described has the potential to be high-throughput. A comparison of Caco-2 samples analyzed both by LC/MS/MS and by automated nanoESI-MS/MS is presented. The permeability and recovery data of the two compounds analyzed in this study obtained from conventional LC/MS/MS and by automated nanoESI-MS/MS were in excellent agreement.
Caco-2 cells offer a means to rapidly screen permeability of drug candidates, allowing pharmaceutical companies to eliminate candidates unable to cross the intestinal barrier early in the discovery process. This screening process is typically performed by conventional liquid chromatography/tandem mass spectrometry (LC/MS/MS), which can require time-consuming method development. An alternative to LC/MS/MS, automated nanoelectrospray tandem mass spectrometry (nanoESI-MS/MS), is introduced. This novel approach requires an off-line ZipTip desalting step followed by automated nanoESI-MS/MS, using the NanoMate 100 and ESI Chip. In addition to reduced method development time, automated nanoESI-MS/MS also offers no carry-over between samples, low sample consumption, and ease-of-use as compared with conventional pulled-capillary nanoelectrospray. Furthermore, the infusion system described has the potential to be high-throughput. A comparison of Caco-2 samples analyzed both by LC/MS/MS and by automated nanoESI-MS/MS is presented. The permeability and recovery data of the two compounds analyzed in this study obtained from conventional LC/MS/MS and by automated nanoESI-MS/MS were in excellent agreement.
Author Korfmacher, Walter A.
Chu, Inhou
Li, Cheng
Van Pelt, Colleen K.
Henion, Jack
Liu, Tongtong
Zhang, Sheng
Fung, Eliza
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Snippet Caco‐2 cells offer a means to rapidly screen permeability of drug candidates, allowing pharmaceutical companies to eliminate candidates unable to cross the...
Caco-2 cells offer a means to rapidly screen permeability of drug candidates, allowing pharmaceutical companies to eliminate candidates unable to cross the...
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SubjectTerms Algorithms
Autoanalysis
Caco-2 Cells - chemistry
Calibration
Cell Membrane Permeability
Chromatography, High Pressure Liquid
Chromatography, Liquid
Drug Evaluation, Preclinical
Humans
Nanotechnology
Robotics
Spectrometry, Mass, Electrospray Ionization
Title A fully automated nanoelectrospray tandem mass spectrometric method for analysis of Caco-2 samples
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