Abstract nr. P1
Ph.d.-studerende
Berit Packert Jensen
Institut for
Analytisk Kemi
Studiestart
1. november 2001
Vejledere
Bente Gammelgaard, Steen Honoré Hansen, DFH
Jan Vanggaard Andersen, Novo Nordisk
Titel på forskningsprojekt
Alternative Detection Principles in Drug Metabolism Studies
- Application of ICP-MS in in vitro and in vivo drug metabolism studies
HPLC-ICP-MS IN DRUG METABOLISM STUDIES
In Drug Discovery and Development there is a demand for an understanding of the metabolism of the drug
candidate. This requires the ability to identify and quantify unknown metabolites from in vitro or in vivo
drug metabolism studies. Identification is often achieved using LC-MS, but for quantitative analysis of
metabolites, MS as well as UV detection are inadequate as the response is dependent on the molecular
structure and authentic standards are rarely available. Furthermore, radiolabelled compounds are normally
not available in the early phase of the projects, and synthesis is expensive and time-consuming. Hence, there
is a need for alternative methods of quantification.
Inductively Coupled Plasma Mass Spectrometry (ICP-MS) is an element specific detection method and the
sensitivity is in principle independent of the structure of the compund. This makes ICP-MS a promising
technique for drug metabolism studies. If a drug contains one of the elements Cl, Br, I or S, the drug
metabolites will show the same molar sensitivity as the drug, provided that they contain the same element in
the same number in the molecule.
For ICP-MS to be of value in metabolism studies, coupling to HPLC is necessary. HPLC implies use of high
concentrations of organic solvents, which is not readily compatible with the ICP-MS instrument. In this
study the influence of solvents on the sensitivities of Cl, Br, I and S in ICP-MS has been investigated. The
use of a membrane desolvator to remove organic solvents will be discussed. An example of application of
HPLC-ICP-MS in drug analysis will be given.