Case Study

Accessing Metabolites of Agrochemical Products

Accessing Metabolites of Agrochemical Products

Metabolites of some agrochemical products such as pesticides and herbicides possess greater plant or mammalian toxicity compared to the parent compound, thus necessitating a need for their identification, study and provision of analytical reference standards to meet regulatory requirements.

Where a synthetic route is challenging, or the identity of a metabolite is unknown, creation of metabolites by microbial biotransformation is often a successful alternative due to similarities of xenobiotic metabolism in mammals, birds, fish, soil, and to some extent, plants.¹ Furthermore, biocatalysis affords aromatic and aliphatic site-selectivity as well as regiocontrol of aromatic hydroxylation.²

Metabolites of the neonicotinoid imidacloprid

In this project, Hypha produced and purified the two active hydroxylated metabolites of the neonicotinoid insecticide imidacloprid, resulting from one of two major mammalian metabolic routes. Use of microbial biotransformation and PolyCYPs enabled both monohydroxylated metabolites to be produced in sufficient quantities. The positional isomers were separated, confirmed by NMR spectroscopy and supplied for use as analytical standards.

imidacloprid metabolites case study image

Metabolites of napropramide

Another case study involved metabolism of the herbicide napropamide. Napropramide is rapidly and extensively metabolized in animals, undergoing sequential hydroxylation and glucuronidation prior to excretion in urine and faeces (EFSA Journal 2010, 8(4): 1565). Napropamide was screened against a panel of Hypha’s biotransforming strains with several hydroxylated metabolites and glucuronides detected by LC-MS. A 0.5L scale-up biotransformation enabled access to milligram quantities of two of the major glucuronides relevant to animal metabolism. Structures were confirmed by NMR spectroscopy as those reported previously as animal metabolites.³

napropamide metabolites case study image

References

1. Schoken, 2000. Pesticide Biotransformation in Plants and Microorganisms, Chapter 3, 30-39.
2. Cusack et al., 2013. Bioorganic and Med. Chem. Letters 23(20), 5471-5483.
3. EFSA Scientific Report 2008, 140: 1-74

Related Resources

Hypha’s microbial biocatalysis process is effective at generating metabolites at up to gram scale. Through Hypha and Selcia’s partnership, [13C], [14C], [2H], [3H] and [15N]-labelled metabolites can be accessed to support regulatory, development or research projects in the pharma and crop protection industries. Hypha establishes optimized processes using unlabelled or stable labelled parent substrates, which can then be transferred to Selcia’s state-of-the-art radiochemistry labs for the production of radiolabelled metabolites.

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