Advances In Sample Preparation For Metabolite Profiling

Nerviano Medical Sciences (NMS) is a new company created following the spin-off by Pfizer of their R&D centre in Nerviano (Milan, Italy). Through its Preclinical Development (PCD) unit, NMS specialises in toxicology, drug metabolism and pharmacokinetics services to pharmaceutical and biotechnology companies. These PCD capabilities are used to support the selection of candidate drugs, predict clinical outcomes from preclinical data (in silico, in vitro, in vivo) and then perform preclinical studies to reduce the attrition rate in the clinic and accelerate the whole drug development process. The extensive experience of drug development of the PCD staff represents a valuable foundation to provide consultancy services on regulatory and scientific programs in any therapeutic areas with unique expertise in oncology.

One of the key stages of the journey of a new chemical entity from initial screening hit, through optimisation, into clinical trials, and ultimately to launch as a new block buster drug, is assessment of the activation pathway and toxicity. These stages are coming under increasing focus as regulatory authorities and patients groups alike are demanding more information about toxic side effects, hence the barrier to launch is raised yet higher. Within every stage of the assessment of the possible new drug, stringent controls are in place to prevent false positive results, or worse still, false negatives. The focus of such controls has traditionally been on the analytical technique and the calibration of systems used. A recent study carried out at Nerviano Medical Sciences in Milan has shown that the sample preparation steps employed can be just as important as the analytical steps in generating errors in the process, and require just as much attention when setting up the process. Critical to the process being established within Nerviano’s laboratory is the evaporation methodology used when preparing the samples.

Project Outline:
The aim of the project was to set up a procedure, based on a semi-preparative LC-MS-MS system to allow the determination of the biological activity and the definitive structure of metabolites taken from in vitro assays or in vivo studies.