The Combination of Electrochemistry and Microfluidic Technology in Drug Metabolism Studies

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.

Keywords: cancer. drug metabolism. electrochemistry; microfluidics; reactive Metabolites.

Figure 1

Different types of metabolites generated in drug metabolism.

Figure 2

Reactive metabolism and cancer.

Figure 3

Important phase I reactive metabolites.

Scheme 1

Steps of drug development.

Figure 4

Electrochemical cell.

Figure 5

Microfluidic cell for mimicking phase I metabolism. The chip structures reproduced from Ref. [95] Copyright (2022), with permission from Royal Society of Chemistry.

Figure 6

Microfluidic electrochemical cells for mimicking phase II metabolism. Chip structure A is reproduced from Ref. [99] under a CC BY licence. Chip structure B reproduced from Ref. [103] copyright (2022) with permission from ACS Publication.