New ultrasensitive detection technologies and techniques for use in microdosing studies.
G. Lappin, C. Wagner, O. Langer, N. C. van de Merbel
Bioanalysis June 11, 2009 DOI: 10.4155/bio.09.40 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | Microdosing |
| Key findings | Reviews three analytical technologies used in microdosing studies: PET, LC-MS/MS, and AMS. PET and AMS employ radioisotopic tracers, with AMS sensitive to ag/ml concentrations, while LC-MS/MS requires no tracer and is sensitive to pg/ml concentrations. |
Abstract
In a microdosing study, subpharmacologically active doses of drug are given to human volunteers at an early stage of development in order to obtain preliminary pharmacokinetic data. The very low doses of drug administered (≤100 µg) consequently lead to very low concentrations of drug appearing in the body and therefore highly sensitive analytical techniques are required. There are three such analytical technologies currently used in microdosing studies: PET, liquid chromatography (LC)-tandem mass spectrometry (MS/MS) and accelerator mass spectrometry (AMS). Both PET and AMS employ radioisotopic tracers. PET is an imaging technique and AMS is an extremely sensitive isotope ratio method, able to measure drug concentrations in the ag/ml range. LC-MS/MS does not require the presence of an isotopic tracer and its sensitivity is in the pg/ml range. This review examines each of these three analytical modalities in the context of performing microdosing studies.