Skip to main content
SpringerLink
Log in

Applications of Targeted Proteomics in ADME for IVIVE

  • Chapter
  • First Online:
Transporters in Drug Development

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

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Abbreviations

ABC:

ATP-binding cassette

ADME:

Absorption, distribution, metabolism, elimination

AQUA:

Absolute quantification

BCRP:

Breast cancer resistance protein (human)

Bcrp:

Breast cancer resistance protein (other species than human)

BLAST:

Basic local alignment search tool

BSEP:

Bile salt export pump (human)

Bsep:

Bile salt export pump (other species than human)

CHAPS:

3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate

CYP:

Cytochrome P450

ELISA:

Enzyme-linked immunosorbent assays

ESI-Q-TOF:

Electrospray ionization quadrupole time of flight

IS:

Internal standard

IVIVE:

In vitro–in vivo extrapolation

LC:

Liquid chromatography

LC-MS/MS:

Liquid chromatography tandem mass spectrometry

MDCK:

Madin–Darby canine kidney

MDR1:

Multidrug resistance protein (P-gp)

MRM:

Multiple reaction monitoring

MRP2:

Multidrug resistance-associated protein 2 (human)

Mrp2:

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

MS:

Mass spectrometry

MSD:

Membrane-spanning domain

NBD:

Nucleotide-binding domain

OATP:

Organic anion-transporting polypeptide

P-gp:

Multidrug resistance protein (MDR1)

PK:

Pharmacokinetics

PSAQ:

Protein standard absolute quantification

PTM:

Posttranslational modifications

RAF:

Relative activity factor

RT-PCR:

Reverse transcription polymerase chain reaction

SCH:

Sandwich-cultured hepatocyte

SDS:

Sodium dodecyl sulfate

SIL:

Stable isotope-labeled

SILAC:

Stable isotope labeling by amino acids in cell culture

SLC:

Solute carrier

SNP:

Single nucleotide polymorphisms

TOF:

Time of flight

WT:

Wild type

References

  • Agarwal N, Lippmann ES, Shusta EV (2010) Identification and expression profiling of blood–brain barrier membrane proteins. J Neurochem 112(3):625–635

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Anderson NL, Jackson A, Smith D, Hardie D, Borchers C, Pearson TW (2009) SISCAPA peptide enrichment on magnetic beads using an in-line bead trap device. Mol Cell Proteomics 8(5): 995–1005

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Arsene CG, Ohlendorf R, Burkitt W et al (2008) Protein quantification by isotope dilution mass spectrometry of proteolytic fragments: cleavage rate and accuracy. Anal Chem 80(11): 4154–4160

    Article  CAS  PubMed  Google Scholar 

  • Balogh LM, Kimoto E, Chupka J, Zhang H, Lai Y (2012) Membrane protein quantification by peptide-based mass spectrometry approaches: Studies on the organic anion-transporting polypeptide family. J Proteomics Bioinform S4:003. doi:10.4172/jpb.S4-003

    Google Scholar 

  • Barr JR, Maggio VL, Patterson DG Jr et al (1996) Isotope dilution–mass spectrometric quantification of specific proteins: model application with apolipoprotein A-I. Clin Chem 42(10): 1676–1682

    CAS  PubMed  Google Scholar 

  • Belinsky MG, Dawson PA, Shchaveleva I et al (2005) Analysis of the in vivo functions of Mrp3. Mol Pharmacol 68(1):160–168

    CAS  PubMed  Google Scholar 

  • Bleasby K, Castle JC, Roberts CJ et al (2006) Expression profiles of 50 xenobiotic transporter genes in humans and pre-clinical species: a resource for investigations into drug disposition. Xenobiotica 36(10–11):963–988

    Article  CAS  PubMed  Google Scholar 

  • Brun V, Dupuis A, Adrait A et al (2007) Isotope-labeled protein standards: toward absolute quantitative proteomics. Mol Cell Proteomics 6(12):2139–2149

    Article  CAS  PubMed  Google Scholar 

  • Brun V, Masselon C, Garin J, Dupuis A (2009) Isotope dilution strategies for absolute quantitative proteomics. J Proteomics 72(5):740–749

    Article  CAS  PubMed  Google Scholar 

  • Chalkley R (2010) Instrumentation for LC-MS/MS in proteomics. Methods Mol Biol 658:47–60

    Article  CAS  PubMed  Google Scholar 

  • Crespi CL, Penman BW (1997) Use of cDNA-expressed human cytochrome P450 enzymes to study potential drug-drug interactions. Adv Pharmacol 43:171–188

    Article  CAS  PubMed  Google Scholar 

  • Deutsch EW, Lam H, Aebersold R (2008) PeptideAtlas: a resource for target selection for emerging targeted proteomics workflows. EMBO Rep 9(5):429–434

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Di L, Whitney-Pickett C, Umland JP et al (2011) Development of a new permeability assay using low-efflux MDCKII cells. J Pharm Sci 100(11):4974–4985

    Article  CAS  PubMed  Google Scholar 

  • Diao L, Li N, Brayman TG, Hotz KJ, Lai Y (2010) Regulation of MRP2/ABCC2 and BSEP/ABCB11 expression in sandwich cultured human and rat hepatocytes exposed to inflammatory cytokines TNF-{alpha}, IL-6, and IL-1{beta}. J Biol Chem 285(41):31185–31192

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Eichacker LA, Granvogl B, Mirus O, Muller BC, Miess C, Schleiff E (2004) Hiding behind hydrophobicity. Transmembrane segments in mass spectrometry. J Biol Chem 279(49): 50915–50922

    Article  CAS  PubMed  Google Scholar 

  • Elliott MH, Smith DS, Parker CE, Borchers C (2009) Current trends in quantitative proteomics. J Mass Spectrom 44(12):1637–1660

    CAS  PubMed  Google Scholar 

  • Elschenbroich S, Kislinger T (2011) Targeted proteomics by selected reaction monitoring mass spectrometry: applications to systems biology and biomarker discovery. Mol Biosyst 7(2): 292–303

    Article  CAS  PubMed  Google Scholar 

  • Elschenbroich S, Kim Y, Medin JA, Kislinger T (2010) Isolation of cell surface proteins for mass spectrometry-based proteomics. Expert Rev Proteomics 7(1):141–154

    Article  CAS  PubMed  Google Scholar 

  • Figge A, Lammert F, Paigen B et al (2004) Hepatic overexpression of murine Abcb11 increases hepatobiliary lipid secretion and reduces hepatic steatosis. J Biol Chem 279(4):2790–2799

    Article  CAS  PubMed  Google Scholar 

  • Geiger T, Wisniewski JR, Cox J, Zanivan S, Kruger M, Ishihama Y, Mann M (2011) Use of stable isotope labeling by amino acids in cell culture as a spike-in standard in quantitative proteomics. Nat Protoc 6(2):147–157

    Article  CAS  PubMed  Google Scholar 

  • Gerber SA, Rush J, Stemman O, Kirschner MW, Gygi SP (2003) Absolute quantification of proteins and phosphoproteins from cell lysates by tandem MS. Proc Natl Acad Sci USA 100(12): 6940–6945

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Ghibellini G, Johnson BM, Kowalsky RJ, Heizer WD, Brouwer KL (2004) A novel method for the determination of biliary clearance in humans. AAPS J 6(4):e33

    Article  PubMed  Google Scholar 

  • Giacomini KM, Huang SM, Tweedie DJ et al (2010) Membrane transporters in drug development. Nat Rev Drug Discov 9(3):215–236

    Article  CAS  PubMed  Google Scholar 

  • Grant KJ, Wu CC (2007) Advances in neuromembrane proteomics: efforts towards a comprehensive analysis of membrane proteins in the brain. Brief Funct Genomic Proteomic 6(1):59–69

    Article  CAS  PubMed  Google Scholar 

  • Haimeur A, Conseil G, Deeley RG, Cole SP (2004) The MRP-related and BCRP/ABCG2 multidrug resistance proteins: biology, substrate specificity and regulation. Curr Drug Metab 5(1):21–53

    Article  CAS  PubMed  Google Scholar 

  • Hanke S, Besir H, Oesterhelt D, Mann M (2008) Absolute SILAC for accurate quantitation of proteins in complex mixtures down to the attomole level. J Proteome Res 7(3):1118–1130

    Article  CAS  PubMed  Google Scholar 

  • Harsha HC, Molina H, Pandey A (2008) Quantitative proteomics using stable isotope labeling with amino acids in cell culture. Nat Protoc 3(3):505–516

    Article  CAS  PubMed  Google Scholar 

  • Haynes PA, Gygi SP, Figeys D, Aebersold R (1998) Proteome analysis: biological assay or data archive? Electrophoresis 19(11):1862–1871

    Article  CAS  PubMed  Google Scholar 

  • Helenius A, McCaslin DR, Fries E, Tanford C (1979) Properties of detergents. Methods Enzymol 56:734–749

    Article  CAS  PubMed  Google Scholar 

  • Ishihama Y, Sato T, Tabata T, Miyamoto N, Sagane K, Nagasu T, Oda Y (2005) Quantitative mouse brain proteomics using culture-derived isotope tags as internal standards. Nat Biotechnol 23(5):617–621

    Article  CAS  PubMed  Google Scholar 

  • Ito K, Uchida Y, Ohtsuki S et al (2011) Quantitative membrane protein expression at the blood–brain barrier of adult and younger cynomolgus monkeys. J Pharm Sci 100(9):3939–3950

    Article  CAS  PubMed  Google Scholar 

  • Iwatsubo T, Suzuki H, Sugiyama Y (1997) Prediction of species differences (rats, dogs, humans) in the in vivo metabolic clearance of YM796 by the liver from in vitro data. J Pharmacol Exp Ther 283(2):462–469

    CAS  PubMed  Google Scholar 

  • Kamiie J, Ohtsuki S, Iwase R et al (2008) Quantitative atlas of membrane transporter proteins: development and application of a highly sensitive simultaneous LC/MS/MS method combined with novel in-silico peptide selection criteria. Pharm Res 25(6):1469–1483

    Article  CAS  PubMed  Google Scholar 

  • Kawakami H, Ohtsuki S, Kamiie J, Suzuki T, Abe T, Terasaki T (2011) Simultaneous absolute quantification of 11 cytochrome P450 isoforms in human liver microsomes by liquid chromatography tandem mass spectrometry with in silico target peptide selection. J Pharm Sci 100(1):341–352

    Article  CAS  PubMed  Google Scholar 

  • Kitamura S, Maeda K, Wang Y, Sugiyama Y (2008) Involvement of multiple transporters in the hepatobiliary transport of rosuvastatin. Drug Metab Dispos 36(10):2014–2023

    Article  CAS  PubMed  Google Scholar 

  • Klammer AA, MacCoss MJ (2006) Effects of modified digestion schemes on the identification of proteins from complex mixtures. J Proteome Res 5(3):695–700

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lai Y (2009) Identification of interspecies difference in hepatobiliary transporters to improve extrapolation of human biliary secretion. Expert Opin Drug Metab Toxicol 5(10):1175–1187

    Article  CAS  PubMed  Google Scholar 

  • Lange V, Picotti P, Domon B, Aebersold R (2008) Selected reaction monitoring for quantitative proteomics: a tutorial. Mol Syst Biol 4:222

    Article  PubMed Central  PubMed  Google Scholar 

  • Langenfeld E, Meyer HE, Marcus K (2008) Quantitative analysis of highly homologous proteins: the challenge of assaying the “CYP-ome” by mass spectrometry. Anal Bioanal Chem 392(6): 1123–1134

    Article  CAS  PubMed  Google Scholar 

  • Lebert D, Dupuis A, Garin J, Bruley C, Brun V (2011) Production and use of stable isotope-labeled proteins for absolute quantitative proteomics. Methods Mol Biol 753:93–115

    Article  CAS  PubMed  Google Scholar 

  • Li N, Nemirovskiy OV, Zhang Y et al (2008) Absolute quantification of multidrug resistance-associated protein 2 (MRP2/ABCC2) using liquid chromatography tandem mass spectrometry. Anal Biochem 380(2):211–222

    Article  CAS  PubMed  Google Scholar 

  • Li N, Bi YA, Duignan DB, Lai Y (2009a) Quantitative expression profile of hepatobiliary transporters in sandwich cultured rat and human hepatocytes. Mol Pharm 6(4):1180–1189

    Article  CAS  PubMed  Google Scholar 

  • Li N, Palandra J, Nemirovskiy OV, Lai Y (2009b) LC-MS/MS mediated absolute quantification and comparison of bile salt export pump and breast cancer resistance protein in livers and hepatocytes across species. Anal Chem 81(6):2251–2259

    Article  CAS  PubMed  Google Scholar 

  • Li N, Zhang Y, Hua F, Lai Y (2009c) Absolute difference of hepatobiliary transporter multidrug resistance-associated protein (MRP2/Mrp2) in liver tissues and isolated hepatocytes from rat, dog, monkey, and human. Drug Metab Dispos 37(1):66–73

    Article  CAS  PubMed  Google Scholar 

  • Li N, Singh P, Mandrell KM, Lai Y (2010) Improved extrapolation of hepatobiliary clearance from in vitro sandwich cultured rat hepatocytes through absolute quantification of hepatobiliary transporters. Mol Pharm 7(3):630–641

    Article  CAS  PubMed  Google Scholar 

  • Lin Y, Zhou J, Bi D, Chen P, Wang X, Liang S (2008) Sodium-deoxycholate-assisted tryptic digestion and identification of proteolytically resistant proteins. Anal Biochem 377(2):259–266

    Article  CAS  PubMed  Google Scholar 

  • Maeda T, Irokawa M, Arakawa H et al (2010) Uptake transporter organic anion transporting polypeptide 1B3 contributes to the growth of estrogen-dependent breast cancer. J Steroid Biochem Mol Biol 122(4):180–185

    Article  CAS  PubMed  Google Scholar 

  • Meier Y, Pauli-Magnus C, Zanger UM et al (2006) Interindividual variability of canalicular ATP-binding-cassette (ABC)-transporter expression in human liver. Hepatology 44(1):62–74

    Article  CAS  PubMed  Google Scholar 

  • Michaud GA, Salcius M, Zhou F et al (2003) Analyzing antibody specificity with whole proteome microarrays. Nat Biotechnol 21(12):1509–1512

    Article  CAS  PubMed  Google Scholar 

  • Nam HJ, Jeon J, Kim S (2009) Bioinformatic approaches for the structure and function of membrane proteins. BMB Rep 42(11):697–704

    Article  CAS  PubMed  Google Scholar 

  • Niessen J, Jedlitschky G, Grube M et al (2009) Human platelets express organic anion-transporting peptide 2B1, an uptake transporter for atorvastatin. Drug Metab Dispos 37(5):1129–1137

    Article  CAS  PubMed  Google Scholar 

  • Niessen J, Jedlitschky G, Grube M et al (2010) Expression of ABC-type transport proteins in human platelets. Pharmacogenet Genomics 20(6):396–400

    Article  CAS  PubMed  Google Scholar 

  • Nishimura M, Naito S (2005) Tissue-specific mRNA expression profiles of human ATP-binding cassette and solute carrier transporter superfamilies. Drug Metab Pharmacokinet 20(6): 452–477

    Article  CAS  PubMed  Google Scholar 

  • Obach RS (2001) The prediction of human clearance from hepatic microsomal metabolism data. Curr Opin Drug Discov Devel 4(1):36–44

    CAS  PubMed  Google Scholar 

  • Ohtsuki S, Uchida Y, Kubo Y, Terasaki T (2011) Quantitative targeted absolute proteomics-based ADME research as a new path to drug discovery and development: methodology, advantages, strategy, and prospects. J Pharm Sci 100(9):3547–3559

    Article  CAS  PubMed  Google Scholar 

  • Ong SE, Mann M (2006) A practical recipe for stable isotope labeling by amino acids in cell culture (SILAC). Nat Protoc 1(6):2650–2660

    Article  CAS  PubMed  Google Scholar 

  • Ong SE, Mann M (2007) Stable isotope labeling by amino acids in cell culture for quantitative proteomics. Methods Mol Biol 359:37–52

    Article  CAS  PubMed  Google Scholar 

  • Ong SE, Blagoev B, Kratchmarova I, Kristensen DB, Steen H, Pandey A, Mann M (2002) Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics. Mol Cell Proteomics 1(5):376–386

    Article  CAS  PubMed  Google Scholar 

  • Prakash A, Tomazela DM, Frewen B, Maclean B, Merrihew G, Peterman S, Maccoss MJ (2009) Expediting the development of targeted SRM assays: using data from shotgun proteomics to automate method development. J Proteome Res 8(6):2733–2739

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Proc JL, Kuzyk MA, Hardie DB et al (2010) A quantitative study of the effects of chaotropic agents, surfactants, and solvents on the digestion efficiency of human plasma proteins by trypsin. J Proteome Res 9(10):5422–5437

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Punta M, Forrest LR, Bigelow H, Kernytsky A, Liu J, Rost B (2007) Membrane protein prediction methods. Methods 41(4):460–474

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Qiu H, Wang Y (2008) Quantitative analysis of surface plasma membrane proteins of primary and metastatic melanoma cells. J Proteome Res 7(5):1904–1915

    Article  CAS  PubMed  Google Scholar 

  • Rabilloud T (2009) Membrane proteins and proteomics: love is possible, but so difficult. Electrophoresis 30(suppl 1):S174–S180

    Article  PubMed  Google Scholar 

  • Renton KW (2001) Alteration of drug biotransformation and elimination during infection and inflammation. Pharmacol Ther 92(2–3):147–163

    Article  CAS  PubMed  Google Scholar 

  • Renton KW (2004) Cytochrome P450 regulation and drug biotransformation during inflammation and infection. Curr Drug Metab 5(3):235–243

    Article  CAS  PubMed  Google Scholar 

  • Sakamoto A, Matsumaru T, Ishiguro N et al (2011) Reliability and robustness of simultaneous absolute quantification of drug transporters, cytochrome P450 enzymes, and udp-glucuronosyltranferases in human liver tissue by multiplexed MRM/selected reaction monitoring mode tandem mass spectrometry with nano-liquid chromatography. J Pharm Sci 100(9): 4037–4043

    Article  CAS  PubMed  Google Scholar 

  • Seibert C, Davidson BR, Fuller BJ, Patterson LH, Griffiths WJ, Wang Y (2009) Multiple-approaches to the identification and quantification of cytochromes P450 in human liver tissue by mass spectrometry. J Proteome Res 8(4):1672–1681

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Shawahna R, Uchida Y, Decleves X et al (2011) Transcriptomic and quantitative proteomic analysis of transporters and drug metabolizing enzymes in freshly isolated human brain microvessels. Mol Pharm 8(4):1332–1341

    Article  CAS  PubMed  Google Scholar 

  • Shimada T, Yamazaki H, Mimura M, Inui Y, Guengerich FP (1994) Interindividual variations in human liver cytochrome P-450 enzymes involved in the oxidation of drugs, carcinogens and toxic chemicals: studies with liver microsomes of 30 Japanese and 30 Caucasians. J Pharmacol Exp Ther 270(1):414–423

    CAS  PubMed  Google Scholar 

  • Speers AE, Wu CC (2007) Proteomics of integral membrane proteins–theory and application. Chem Rev 107(8):3687–3714

    Article  CAS  PubMed  Google Scholar 

  • Sui P, Miliotis T, Davidson M, Karlsson R, Karlsson A (2011) Membrane protein digestion—comparison of LPI HexaLane with traditional techniques. Methods Mol Biol 753:129–142

    Article  CAS  PubMed  Google Scholar 

  • Sun D, Lennernas H, Welage LS et al (2002) Comparison of human duodenum and Caco-2 gene expression profiles for 12,000 gene sequences tags and correlation with permeability of 26 drugs. Pharm Res 19(10):1400–1416

    Article  CAS  PubMed  Google Scholar 

  • Tanaka Y, Slitt AL, Leazer TM, Maher JM, Klaassen CD (2005) Tissue distribution and hormonal regulation of the breast cancer resistance protein (Bcrp/Abcg2) in rats and mice. Biochem Biophys Res Commun 326(1):181–187

    Article  CAS  PubMed  Google Scholar 

  • Teng S, Piquette-Miller M (2005) The involvement of the pregnane X receptor in hepatic gene regulation during inflammation in mice. J Pharmacol Exp Ther 312(2):841–848

    Article  CAS  PubMed  Google Scholar 

  • Uchida Y, Ohtsuki S, Katsukura Y, Ikeda C, Suzuki T, Kamiie J, Terasaki T (2011a) Quantitative targeted absolute proteomics of human blood–brain barrier transporters and receptors. J Neurochem 117(2):333–345

    Article  CAS  PubMed  Google Scholar 

  • Uchida Y, Ohtsuki S, Kamiie J, Terasaki T (2011b) Blood–brain barrier (BBB) pharmacoproteomics (PPx): reconstruction of in vivo brain distribution of 11 P-glycoprotein substrates based on the BBB transporter protein concentration, in vitro intrinsic transport activity, and unbound fraction in plasma and brain in mice. J Pharmacol Exp Ther 339(2):579–588

    Article  CAS  PubMed  Google Scholar 

  • Vander Borght S, Libbrecht L, Katoonizadeh A et al (2006) Breast cancer resistance protein (BCRP/ABCG2) is expressed by progenitor cells/reactive ductules and hepatocytes and its expression pattern is influenced by disease etiology and species type: possible functional consequences. J Histochem Cytochem 54(9):1051–1059

    Article  CAS  PubMed  Google Scholar 

  • Whitelegge J, Halgand F, Souda P, Zabrouskov V (2006) Top-down mass spectrometry of integral membrane proteins. Expert Rev Proteomics 3(6):585–596

    Article  CAS  PubMed  Google Scholar 

  • Wu CC, Yates JR III (2003) The application of mass spectrometry to membrane proteomics. Nat Biotechnol 21(3):262–267

    Article  CAS  PubMed  Google Scholar 

  • Wu CC, MacCoss MJ, Howell KE, Yates JR III (2003) A method for the comprehensive proteomic analysis of membrane proteins. Nat Biotechnol 21(5):532–538

    Article  CAS  PubMed  Google Scholar 

  • Yocum AK, Chinnaiyan AM (2009) Current affairs in quantitative targeted proteomics: multiple reaction monitoring-mass spectrometry. Brief Funct Genomic Proteomic 8(2):145–157

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang G, Fenyo D, Neubert TA (2009) Evaluation of the variation in sample preparation for comparative proteomics using stable isotope labeling by amino acids in cell culture. J Proteome Res 8(3):1285–1292

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang G, Annan RS, Carr SA, Neubert TA (2010) Overview of peptide and protein analysis by mass spectrometry. Curr Protoc Protein Sci. Chapter 16:Unit16.11

    Google Scholar 

  • Zhang Y, Li N, Brown PW, Ozer JS, Lai Y (2011) Liquid chromatography/tandem mass spectrometry based targeted proteomics quantification of P-glycoprotein in various biological samples. Rapid Commun Mass Spectrom 25(12):1715–1724

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pfizer Global Research and Development, Groton, CT, USA

    Larissa M. Balogh & Yurong Lai

Authors
  1. Larissa M. Balogh
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yurong Lai
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Larissa M. Balogh .

Editor information

Editors and Affiliations

  1. The University of Tokyo Graduate School of Pharmac. Sciences, Tokyo, Japan

    Yuichi Sugiyama

  2. Pharma, Drug Transporters in ADME Department of Pharmacy, University of Copenhagen Faculty of Health and Medical Sciences, Copenhagen, Denmark

    Bente Steffansen

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Balogh, L.M., Lai, Y. (2013). Applications of Targeted Proteomics in ADME for IVIVE. In: Sugiyama, Y., Steffansen, B. (eds) Transporters in Drug Development. AAPS Advances in the Pharmaceutical Sciences Series, vol 7. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8229-1_5

Download citation

Publish with us

Policies and ethics

Search

Navigation