Applications of Targeted Proteomics in ADME for IVIVE

Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 7)


Membrane transporters act as physiological “gatekeepers” that regulate the distribution of endogenous and exogenous compounds. It is therefore imperative that drug discovery/development research considers the function and expression of drug transporters, which can dictate drug concentration to pharmacological targets or may be the drug target themselves. Variation in transporter expression across species and in vitro models is recognized as a major complicating factor encountered during in vitro–in vivo extrapolations that can limit a model’s predictive power. This is particularly problematic in scenarios such as biliary secretion that are dependent upon in vitro and preclinical data due to lack of clinical bile samples. Consequently, quantification of drug transport proteins becomes a fundamental element in establishing important correlations for pharmacokinetic predictions that are of significant interest during drug discovery. In this chapter we provide an overview of methodologies relevant to protein quantification and their important limitations, followed by a review of recent studies in which mass spectrometry-based targeted quantifications of drug transporters are applied in predictions of transporter-mediated drug clearance.


Single Nucleotide Polymorphism Breast Cancer Resistance Protein Digestion Efficiency Bile Salt Export Pump Sample Preparation Condition 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



ATP-binding cassette


Absorption, distribution, metabolism, elimination


Absolute quantification


Breast cancer resistance protein (human)


Breast cancer resistance protein (other species than human)


Basic local alignment search tool


Bile salt export pump (human)


Bile salt export pump (other species than human)




Cytochrome P450


Enzyme-linked immunosorbent assays


Electrospray ionization quadrupole time of flight


Internal standard


In vitro–in vivo extrapolation


Liquid chromatography


Liquid chromatography tandem mass spectrometry


Madin–Darby canine kidney


Multidrug resistance protein (P-gp)


Multiple reaction monitoring


Multidrug resistance-associated protein 2 (human)


Multidrug resistance-associated protein 2 (other species than human)


Mass spectrometry


Membrane-spanning domain


Nucleotide-binding domain


Organic anion-transporting polypeptide


Multidrug resistance protein (MDR1)




Protein standard absolute quantification


Posttranslational modifications


Relative activity factor


Reverse transcription polymerase chain reaction


Sandwich-cultured hepatocyte


Sodium dodecyl sulfate


Stable isotope-labeled


Stable isotope labeling by amino acids in cell culture


Solute carrier


Single nucleotide polymorphisms


Time of flight


Wild type


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Pfizer Global Research and DevelopmentGrotonUSA

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