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Making Metabolites

A four-year research project is underway at Industrial Research Ltd in Wellington to investigate the feasibility of using liver enzymes to make the metabolites used as reference standards in drug testing.

In processing foreign substances, the liver produces metabolites which are more easily excreted from the body; the presence of these metabolites can act as a marker for the original substance. Most metabolites used in testing are created through chemical processes.

Scientist David Stevenson says there is a continuing need for metabolites to match new drugs. The metabolites act as reference standards for laboratories to ensure accurate identification of substances and to calibrate equipment. These materials are needed in small quantities, but sometimes it is too difficult and too expensive to make the metabolites using conventional chemical methods.

"Although we're talking about very small quantities of very high value, one gram of a particular metabolite could be a year's supply for the whole planet," he says. And the value of that gram could be as much as US$750,000.

He says enzymatic synthesis, using natural enzymes found in the livers of animals such as sheep, pigs and cattle, could not only reduce the cost of making metabolites, but also produce compounds not accessible by chemical methods.

Six months into the project, Stevenson has already produced, on a small scale, a glucuronide metabolite compound which no one has been able to make chemically before. He is also making a glucuronide for HortResearch to test a flavour compound found in fruit and vegetables.

While the primary use for the enzymatically produced metabolites will be in dope-testing athletes, drug abusers and racehorses, other potential uses include products for medical research such as metabolites of hormones, carcinogens, toxins and pollutants, and for analysis of animal pharmaceutical residues in meat and milk.

IRL is working with New Zealand company B. Dent Global, a manufacturer and distributor of testing standards, who will commercialise any successful research.