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Solid-Phase Microextraction in Binding Studies

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Solid Phase Microextraction
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Abstract

This chapter briefly discusses how solid-phase microextraction (SPME) can be successfully implemented to accurately measure ligand–receptor binding constants, % plasma protein binding, blood-to-plasma distribution ratios, and free versus total analyte concentrations. The main practical considerations and assumptions to successfully apply SPME to binding studies are discussed in detail, including the effect of significant versus negligible depletion, extraction time, pH, and fiber fouling. The binding results obtained with SPME are compared to literature values and to other techniques used for binding determinations, and the advantages and disadvantages of different methods are clearly discussed. Recent applications of SPME in binding studies are highlighted, with the primary focus on binding studies in biological fluids and tissues since this application area is where SPME has been most extensively applied. Highlighted examples show that SPME has been successfully applied for ligands with both low and high binding affinities, for ligands with different affinities to multiple sites on a given receptor, to study differences in inter-species binding as well as partitioning coefficients for various tissue types. The importance of studying inter-individual variability of free concentrations in future studies is highlighted and can contribute to the development of personalized medicine.

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References

  1. Zhang F, Xue J, Shao J et al (2012) Compilation of 222 drugs’ plasma protein binding data and guidance for study designs. Drug Discov Today 17(9–10):475–485. doi:10.1016/j.drudis.2011.12.018

    Article  CAS  Google Scholar 

  2. Vuignier K, Schappler J, Veuthey J et al (2010) Drug-protein binding: a critical review of analytical tools. Anal Bioanal Chem 398(1):53–66. doi:10.1007/s00216-010-3737-1

    Article  CAS  Google Scholar 

  3. Illamola SM, Hirt D, Tréluyer JM et al (2015) Challenges regarding analysis of unbound fraction of highly bound protein antiretroviral drugs in several biological matrices: lack of harmonisation and guidelines. Drug Discov Today 20(4):466–474. doi:10.1016/j.drudis.2014.11.010

    Article  CAS  Google Scholar 

  4. Musteata FM, Pawliszyn J (2005) Study of ligand–receptor binding using SPME: investigation of receptor, free, and total ligand concentrations. J Proteome Res 4(3):789–800. doi:10.1021/pr049768z

  5. Musteata FM, Pawliszyn J (2005) Assay of stability, free and total concentration of chlorhexidine in saliva by solid phase microextraction. J Pharm Biomed Anal 37(5):1015–1024. http://dx.doi.org/10.1016/j.jpba.2004.09.055

  6. Vuckovic D, Pawliszyn J (2009) Automated study of ligand–receptor binding using solid-phase microextraction. J Pharm Biomed Anal 50(4):550–555. doi:10.1016/j.jpba.2008.08.023

  7. Vuckovic D, Cudjoe E, Musteata FM et al (2010) Automated solid-phase microextraction and thin-film microextraction for high-throughput analysis of biological fluids and ligand–receptor binding studies. Nat Protoc 5:140–161. doi:10.1038/nprot.2009.180

  8. Heringa MB, Hermens JLM (2003) Measurement of free concentrations using negligible depletion-solid phase microextraction (nd-SPME). TrAC Trends Anal Chem 22(10):575–587. http://dx.doi.org/10.1016/S0165-9936(03)01006-9

  9. Zhang X, Oakes KD, Hoque ME et al (2011) Pre-equilibrium solid-phase microextraction of free analyte in complex samples: correction for mass transfer variation from protein binding and matrix tortuosity. Anal Chem 83(9):3365–3370. doi:10.1021/ac2004899

    Article  CAS  Google Scholar 

  10. Peltenburg H, Bosman IJ, Hermens JLM (2015) Sensitive determination of plasma protein binding of cationic drugs using mixed-mode solid-phase microextraction. J Pharm Biomed Anal 115:534–542. doi:10.1016/j.jpba.2015.08.002

    Article  CAS  Google Scholar 

  11. Heringa MB, Hogevonder C, Busser F et al (2006) Measurement of the free concentration of octylphenol in biological samples with negligible depletion-solid phase microextraction (nd-SPME): analysis of matrix effects. J Chromatogr B 834(1–2):35–41. http://dx.doi.org/10.1016/j.jchromb.2006.02.009

  12. Oomen AG, Mayer P, Tolls J (2000) Nonequilibrium solid-phase microextraction for determination of the freely dissolved concentration of hydrophobic organic compounds: matrix effects and limitations. Anal Chem 72(13):2802–2808. doi:10.1021/ac9914162

    Article  CAS  Google Scholar 

  13. Hulme EC, Trevethick MA (2010) Ligand binding assays at equilibrium: validation and interpretation. Br J Pharmacol 161(6):1219–1237. doi:10.1111/j.1476-5381.2009.00604.x

    Article  CAS  Google Scholar 

  14. Alam MN, Ricardez-Sandoval L, Pawliszyn J (2015) Numerical modeling of solid-phase microextraction: binding matrix effect on equilibrium time. Anal Chem 87(19):9846–9854. doi:10.1021/acs.analchem.5b02239

    Article  CAS  Google Scholar 

  15. Broeders JJW, Blaauboer BJ, Hermens JLM (2011) Development of a negligible depletion-solid phase microextraction method to determine the free concentration of chlorpromazine in aqueous samples containing albumin. J Chromatogr A 1218(47):8529–8535. doi:10.1016/j.chroma.2011.09.064

    Article  CAS  Google Scholar 

  16. Bojko B, Vuckovic D, Pawliszyn J (2012) Comparison of solid phase microextraction versus spectroscopic techniques for binding studies of carbamazepine. J Pharm Biomed Anal 66:91–99. doi:10.1016/j.jpba.2012.03.005

  17. Musteata FM, Pawliszyn J (2006) Determination of free concentration of paclitaxel in liposome formulations. J Pharm Pharm Sci 9(2):231–237

    Google Scholar 

  18. Nilsson LB (2013) The bioanalytical challenge of determining unbound concentration and protein binding for drugs. Bioanalysis 5(24):3033–3050. doi:10.4155/bio.13.274

    Article  CAS  Google Scholar 

  19. Musteata FM, Pawliszyn J, Qian MG et al (2006) Determination of drug plasma protein binding by solid phase microextraction. J Pharm Sci 95(8):1712–1722. http://0-dx.doi.org.mercury.concordia.ca/10.1002/jps.20558

  20. Musteata FM (2012) Ligand–receptor binding and determination of free concentrations. In: Pawliszyn J (ed) Anonymous handbook of solid phase microextraction. Elsevier, pp 383–397. doi:10.1016/B978-0-12-416017-0.00011-5

  21. Buscher B, Laakso S, Mascher H et al (2014) Bioanalysis for plasma protein binding studies in drug discovery and drug development: views and recommendations of the European bioanalysis forum. Bioanalysis 6(5):673–682. doi:10.4155/bio.13.338

    Article  CAS  Google Scholar 

  22. Bessonneau V, Zhan Y, De Lannoy IAM et al (2015) In vivo solid-phase microextraction liquid chromatography-tandem mass spectrometry for monitoring blood eicosanoids time profile after lipopolysaccharide-induced inflammation in Sprague-Dawley rats. J Chromatogr A 1424:134–138. doi:10.1016/j.chroma.2015.10.067

    Article  CAS  Google Scholar 

  23. Birjandi AP, Mirnaghi FS, Bojko B et al (2014) Application of solid phase microextraction for quantitation of polyunsaturated fatty acids in biological fluids. Anal Chem 86(24):12022–12029. doi:10.1021/ac502627w

    Article  CAS  Google Scholar 

  24. Wu Q, Wu D, Guan Y (2013) In vivo fast equilibrium microextraction by stable and biocompatible nanofiber membrane sandwiched in microfluidic device. Anal Chem 85(23):11524–11531. doi:10.1021/ac4028438

    Article  CAS  Google Scholar 

  25. Wu Q, Wu D, Guan Y (2013) Fast equilibrium micro-extraction from biological fluids with biocompatible core–sheath electrospun nanofibers. Anal Chem 85(12):5924–5932. doi:10.1021/ac4006974

    Article  CAS  Google Scholar 

  26. Vuckovic D, Gien B, de Lannoy I et al (2011) In vivo solid-phase microextraction for single rodent pharmacokinetics studies of carbamazepine and carbamazpine-10,11-epoxide in mice. J Chromatogr A 1218:3367–3375. doi:10.1016/j.chroma.2010.07.060

  27. Artola-Garciano E, Vaes WHJ, Hermens JLM (2000) Validation of negligible depletion solid-phase microextraction as a tool to determine tissue/blood partition coefficients for semivolatile and nonvolatile organic chemicals. Toxicol Appl Pharmacol 166:138–144. doi:10.1006/taap.2000.8969

  28. Heringa MB, Pastor D, Algra J et al (2002) Negligible depletion solid-phase microextraction with radiolabeled analytes to study free concentrations and protein binding: an example with [3H]estradiol. Anal Chem 74:5993–5997. doi:10.1021/ac0204552

  29. Zhou F, Zhao M, Su G et al (2014) Binding of aroma compounds with myofibrillar proteins modified by a hydroxyl-radical-induced oxidative system. J Agric Food Chem 62(39):9544–9552. doi:10.1021/jf502540p

    Article  CAS  Google Scholar 

  30. Kühn J, Zhu X-, Considine T et al (2007) Binding of 2-nonanone and milk proteins in aqueous model systems. J Agric Food Chem 55(9):3599–3604. doi:10.1021/jf063517o

    Article  Google Scholar 

  31. Prosen H, Fingler S, Zupančič-Kralj L et al (2007) Partitioning of selected environmental pollutants into organic matter as determined by solid-phase microextraction. Chemosphere 66(8):1580–1589. doi:10.1016/j.chemosphere.2006.08.006

  32. Bandow N, Altenburger R, Brack W (2010) Application of nd-SPME to determine freely dissolved concentrations in the presence of green algae and algae-water partition coefficients. Chemosphere 79(11):1070–1076. doi:10.1016/j.chemosphere.2010.03.021

    Article  CAS  Google Scholar 

  33. Alix A, Collot D, Nénon J- et al (2001) Measurement of insecticide uptake and effective fraction in a beneficial insect using solid-phase microextraction. Anal Chem 73(13):3107–3111. doi:10.1021/ac0013148

    Article  CAS  Google Scholar 

  34. Chalumot G, Yao C, Pino V et al (2009) Determining the stoichiometry and binding constants of inclusion complexes formed between aromatic compounds and β-cyclodextrin by solid-phase microextraction coupled to high-performance liquid chromatography. J Chromatogr A 1216(27):5242–5248. doi:10.1016/j.chroma.2009.05.017

    Article  CAS  Google Scholar 

  35. Bojko B, Vuckovic D, Cudjoe E et al (2011) Determination of tranexamic acid concentration by solid phase microextraction and liquid chromatography-tandem mass spectrometry: first step to in vivo analysis. J Chromatogr B Anal Tech Biomed Life Sci 879(32):3781–3787. doi:10.1016/j.jchromb.2011.08.003

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Correspondence to Dajana Vuckovic .

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Vuckovic, D. (2017). Solid-Phase Microextraction in Binding Studies. In: Ouyang, G., Jiang, R. (eds) Solid Phase Microextraction. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-53598-1_10

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