Electrochemical HPLC Systems Help in Medical Chemistry and Drug Metabolism Studies

High performance liquid chromatography (HPLC) systems were developed to support medical chemistry and help drug-metabolism studies. These systems enable significant quantities of difficult-to-obtain metabolites from a variety of parent compounds to be electrosynthesized.

New, high-efficiency, high-capacity electrochemical-synthesis cells are present at the systems' core. The user can control oxidation capability to generate specific oxidation products. This enhances laboratories' ability to perform a variety of metabolite-generation tasks, alleviating the need to deploy medicinal chemistry resources to support drug-metabolism identification.

Assessing metabolic stability and correctly identifying a compound's metabolites using various in vitro and in vivo drug-metabolism assays are crucial steps in determining a compound's suitability for drug development. However, liquid chromatography-mass spectrometry (LC-MS), the system used for metabolism studies, only reports the molecular weight of the metabolites being examined. LC-MS cannot easily determine the exact structure of a given metabolite, especially if one or more hydroxylation reactions are involved in the metabolism of the compound.

Developed and launched by ESA (Chelmsford, MA, USA), the new electrochemical (EC) HPLC system has two cells to suit specific application needs--the 5150 cell, which has high capacity and is preferred for low-potential (< 500 mV) oxidation reactions, and the 5125 cell, which is recommended for high-potential reactions. The smaller volume 5125 cell minimizes unwanted over-oxidation reactions.

Dr. Darwin Asa, ESA director of HPLC marketing, said, "ESA's new electrochemical synthesis systems are an ideal complement to LC-MS for ADME-Tox/ DMPK [adsorption, distribution, metabolism, elimination toxicity] operations. Of particular interest to scientists evaluating the metabolic properties and toxicity of potential drugs, these systems mimic much of the oxidation capabilities of cytochrome p450, a key enzyme family that is responsible for metabolizing most drugs. Drug interactions involving the cytochrome p450 system are common, and a major cause of attrition in the drug-development process. Understanding the metabolites generated by these enzymes is key to understanding a compound's metabolic fate.”


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