High-throughput Caco-2 cell permeability screening by cassette dosing and sample pooling approaches using direct injection/on-line guard cartridge extraction/tandem mass spectrometry

Bu, Hai‐Zhi; Poglod, Marzena; Micetich, Ronald G.; Khan, Jehangir K.

doi:10.1002/(sici)1097-0231(20000331)14:6<523::aid-rcm906>3.0.co;2-t

Cited by 66 publications

(41 citation statements)

References 15 publications

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“…The highthroughput Caco-2 permeability screening method for drug candidates was developed using a similar simple column switching system. 171 The apparent permeability coefficients of tested drugs across Caco-2 cell monolayers were in good conformity with data obtained by the single dosing method. The in vitro model based on filter-immobilized artificial membranes has also been developed as a more simple method than the use of Caco-2 cell monolayers for fast screening of drug candidates.…”

Section: ·2 Drug Metabolismsupporting

confidence: 74%

Biomedical and Biological Mass Spectrometry

Mano

Goto

2003

ANAL. SCI.

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By the end of the 20th century, mass spectrometry (MS) had evolved drastically as a major analytical tool in biomedical and biological research. Recent mass spectrometers, designed for ease of handling, came into wide use in the 1990s. Soft ionization methods, which were made practical in the second half of the 1980s, allowed for the sensitive analysis of nonvolatile and thermolabile compounds by MS. Electrospray ionization (ESI) 1,2 and matrix-assisted laser desorption ionization (MALDI) 3 methods, made it possible to ionize large biomolecules and to transfer them to the gas phase, thereby becoming a valuable tool in both protein and peptide analysis [4][5][6] and in the study of drugs and their metabolites [7][8][9][10][11][12] in the human body. Many reviews of MS have recently been published, [13][14][15][16][17][18][19] and in particular, the number of reviews describing biochemical, biological, and biomedical MS have increased dramatically over the last ten years. Initially, there were many commentary reviews on new techniques, such as soft ionization methods and mass analyzers, 13-15 and more recently, review articles have focused on the biological and biomedical applications of MS. 18-21 Above all, two major fields, drug discovery and proteomics, have made marked advances based on MS.Articles in the MEDLINE database were searched, and the results are illustrated in Fig. 1 and Table 1. Over the last 15 years, a total of 79220 MS articles were placed in the database, with a 2.5-fold increase from 1987 to 1999. The number of articles using fast atom bombardment (FAB) as an ionization method remained almost constant during this period. This ionization method is a practical soft ionization procedure, which was applied to the analysis of peptides [22][23][24][25][26][27][28][29][30][31] and endogenous biological substances [32][33][34][35] in the 1980s. Atmospheric pressure chemical ionization (APCI) is a suitable method 36 for the ionization of middle or weakly polar low-molecular-weight molecules, and can be easily coupled to conventional highperformance liquid chromatography (HPLC), used at a flow rate of around 1 mL/min. [37][38][39][40][41][42][43][44][45][46][47][48] However, the number of articles concerning APCI have increased slowly, because most drugs developed recently contain polar groups which can be ionized without difficulty by the ESI technique. Japan This review focuses on biological and biomedical mass spectrometry, and covers a selection of publications in this area included in the MEDLINE database for the period 1987 -2001. Over the last 15 years, biological and biomedical mass spectrometry has progressed out of all recognition. The development of soft ionization methods, such as electrospray ionization and matrix-assisted laser desorption ionization, has mainly contributed to the remarkable progress, because they can easily produce gas-phase ions of large, polar, and thermally labile biomolecules, such as proteins, peptides, nucleic acids and others. The innovations of ionization meth...

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Section: ·2 Drug Metabolismsupporting

confidence: 74%

Biomedical and Biological Mass Spectrometry

Mano

Goto

2003

ANAL. SCI.

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“…Liquid chromatography coupled with tandem mass spectrometry (LC/MS/MS), due to its superior sensitivity, selectivity, and rapidity along with significantly reduced method development time, is an ideal analytical tool for high-throughput analysis of transport samples. In addition, the exceptional capability of LC/MS/MS for the simultaneous determination of multiple drug mixtures has allowed sample pooling (i.e., multiple samples to be pooled before analysis), which forms the throughput of the monolayer transport assay (Bu et al, 2000).…”

Section: Methods For Assessing Drug Transporter Activities In Drumentioning

confidence: 99%

Impact of Drug Transporter Studies on Drug Discovery and Development

et al. 2003

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“…The most common cell monolayer is the Caco-2 cell line, which is a polarized human colonic cancer cell line that forms integral monolayers and TJs when grown for ∼20 days. These cells can be grown in 6-, 12-, 24-, and 96-well plate formats, which lend themselves well to robotic automation for both seeding and feeding, and permeability measurements [100,101]. Transcellular permeability is the movement of the compound through the cell itself and is often referred to as passive permeability; it is the parameter of most interest at the early screening stage.…”

Section: Permeabilitymentioning

confidence: 99%

Oral Absorption: from Physiology to Regulatory

Berlioz‐Seux

2012

Encyclopedia of Drug Metabolism and Interactions

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Intestinal absorption consists of the sum of multiple processes. First, solubility, dissolution rate, lipophilicity, p K a (negative logarithm of the acid dissociation constant, K a ), and molecular weight (MW) are major physicochemical properties driving the absorption potential of a drug. The drug's permeability is a major determinant of its ability to be absorbed in the intestine. Intestinal absorption can occur through different mechanisms. Within the “rule of 5” chemical space, drugs are usually absorbed through a passive process. Also, intestinal transporters could either hinder or promote a molecule's absorption and can lead to drug‐drug interactions (DDIs). In vitro and in vivo tools exist to study intestinal absorption. These tools provide data with different degrees of granularity and with distinct human absorption predictability. Finally, the Food and Drug Administration (FDA) has developed guidelines to assess molecules' properties in terms of intestinal absorption and potential of DDIs.

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High-throughput Caco-2 cell permeability screening by cassette dosing and sample pooling approaches using direct injection/on-line guard cartridge extraction/tandem mass spectrometry

Cited by 66 publications

References 15 publications

Biomedical and Biological Mass Spectrometry

Biomedical and Biological Mass Spectrometry

Impact of Drug Transporter Studies on Drug Discovery and Development

Oral Absorption: from Physiology to Regulatory

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