The Combination of Electrochemistry and Microfluidic Technology in Drug Metabolism Studies

Overview

Journal ChemistryOpen

Specialty Chemistry

Date 2022 Sep 27

PMID 36166688

Authors

Isobel Grint

Francesco Crea

Rafaela Vasiliadou

Affiliations

Soon will be listed here.

Abstract

Drugs are metabolized within the liver (pH 7.4) by phase I and phase II metabolism. During the process, reactive metabolites can be formed that react covalently with biomolecules and induce toxicity. Identifying and detecting reactive metabolites is an important part of drug development. Preclinical and clinical investigations are conducted to assess the toxicity and safety of a new drug candidate. Electrochemistry coupled to mass spectrometry is an ideal complementary technique to the current preclinical studies, a pure instrumental approach without any purification steps and tedious protocols. The combination of microfluidics with electrochemistry towards the mimicry of drug metabolism offers portability, low volume of reagents and faster reaction times. This review explores the development of microfluidic electrochemical cells for mimicking drug metabolism.

Citing Articles

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PMID: 38930787 PMC: 11205554. DOI: 10.3390/molecules29122721.

The Combination of Electrochemistry and Microfluidic Technology in Drug Metabolism Studies.

Grint I, Crea F, Vasiliadou R ChemistryOpen. 2022; 11(12):e202200100.

PMID: 36166688 PMC: 9716038. DOI: 10.1002/open.202200100.

References

Goldner V, Fangmeyer J, Karst U . Development of an electrochemical flow-through cell for the fast and easy generation of isotopically labeled metabolite standards. Drug Test Anal. 2021; 14(2):262-268. DOI: 10.1002/dta.3175. View

Pereira S, Bertolino F, Fernandez-Baldo M, Messina G, Salinas E, Sanz M . A microfluidic device based on a screen-printed carbon electrode with electrodeposited gold nanoparticles for the detection of IgG anti-Trypanosoma cruzi antibodies. Analyst. 2011; 136(22):4745-51. DOI: 10.1039/c1an15569e. View

Mistry K, Layek K, Mahapatra A, RoyChaudhuri C, Saha H . A review on amperometric-type immunosensors based on screen-printed electrodes. Analyst. 2014; 139(10):2289-311. DOI: 10.1039/c3an02050a. View

Grint I, Crea F, Vasiliadou R . The Combination of Electrochemistry and Microfluidic Technology in Drug Metabolism Studies. ChemistryOpen. 2022; 11(12):e202200100. PMC: 9716038. DOI: 10.1002/open.202200100. View

Xu C, Li C, Kong A . Induction of phase I, II and III drug metabolism/transport by xenobiotics. Arch Pharm Res. 2005; 28(3):249-68. DOI: 10.1007/BF02977789. View

Stalder R, Roth G . Preparative microfluidic electrosynthesis of drug metabolites. ACS Med Chem Lett. 2014; 4(11):1119-23. PMC: 4027460. DOI: 10.1021/ml400316p. View

Baumann A, Karst U . Online electrochemistry/mass spectrometry in drug metabolism studies: principles and applications. Expert Opin Drug Metab Toxicol. 2010; 6(6):715-31. DOI: 10.1517/17425251003713527. View

Kalgutkar A, Henne K, Lame M, Vaz A, Collin C, Soglia J . Metabolic activation of the nontricyclic antidepressant trazodone to electrophilic quinone-imine and epoxide intermediates in human liver microsomes and recombinant P4503A4. Chem Biol Interact. 2005; 155(1-2):10-20. DOI: 10.1016/j.cbi.2005.03.036. View

Jung E, Maibach H . Animal models for percutaneous absorption. J Appl Toxicol. 2014; 35(1):1-10. DOI: 10.1002/jat.3004. View

10.

Fura A . Role of pharmacologically active metabolites in drug discovery and development. Drug Discov Today. 2006; 11(3-4):133-42. DOI: 10.1016/S1359-6446(05)03681-0. View

11.

Brandon E, Raap C, Meijerman I, Beijnen J, Schellens J . An update on in vitro test methods in human hepatic drug biotransformation research: pros and cons. Toxicol Appl Pharmacol. 2003; 189(3):233-46. DOI: 10.1016/s0041-008x(03)00128-5. View

12.

Hayes J, Flanagan J, Jowsey I . Glutathione transferases. Annu Rev Pharmacol Toxicol. 2005; 45:51-88. DOI: 10.1146/annurev.pharmtox.45.120403.095857. View

13.

Wang W, Ballatori N . Endogenous glutathione conjugates: occurrence and biological functions. Pharmacol Rev. 1998; 50(3):335-56. View

14.

Steinmetz K, Spack E . The basics of preclinical drug development for neurodegenerative disease indications. BMC Neurol. 2009; 9 Suppl 1:S2. PMC: 2697630. DOI: 10.1186/1471-2377-9-S1-S2. View

15.

Gomez-Lechon M, Donato T, Ponsoda X, Castell J . Human hepatic cell cultures: in vitro and in vivo drug metabolism. Altern Lab Anim. 2004; 31(3):257-65. DOI: 10.1177/026119290303100307. View

16.

van den Brink F, Buter L, Odijk M, Olthuis W, Karst U, van den Berg A . Mass spectrometric detection of short-lived drug metabolites generated in an electrochemical microfluidic chip. Anal Chem. 2014; 87(3):1527-35. DOI: 10.1021/ac503384e. View

17.

Rubino F . Toxicity of Glutathione-Binding Metals: A Review of Targets and Mechanisms. Toxics. 2017; 3(1):20-62. PMC: 5634692. DOI: 10.3390/toxics3010020. View

18.

Macpherson J . A practical guide to using boron doped diamond in electrochemical research. Phys Chem Chem Phys. 2014; 17(5):2935-49. DOI: 10.1039/c4cp04022h. View

19.

Vasiliadou R, Esfahani M, Brown N, Welham K . A Disposable Microfluidic Device with a Screen Printed Electrode for Mimicking Phase II Metabolism. Sensors (Basel). 2016; 16(9). PMC: 5038696. DOI: 10.3390/s16091418. View

20.

Chira R, Fangmeyer J, Neaga I, Zaharia V, Karst U, Bodoki E . Simulation of the oxidative metabolization pattern of netupitant, an NK receptor antagonist, by electrochemistry coupled to mass spectrometry. J Pharm Anal. 2021; 11(5):661-666. PMC: 8572700. DOI: 10.1016/j.jpha.2021.03.011. View