Drugs and other xenobiotics entering the body are generally subject to metabolism that facilitates their detoxification and elimination. The ability to predict the metabolic fate of compounds before the first doses are given to humans is highly desirable for reasons of both efficacy and safety. However, the size of the animal models usually restricts the sample volume that can be safely taken during a pharmacokinetic time study for the drug and its metabolites. This quickly results in the need for many animals and a significant amount of drug material. Discovery-stage PK studies can be cost prohibitive, especially when using rare and expensive mouse strains. Therefore, an analytical system capable of producing the maximum data from a small sample volume is highly desirable to maximize scientific information and reduce animal usage. Reduction of animal usage in discovery-stage PK studies it is possible by using microsampling-based approaches (serial sampling for single mouse), but an increase in sensitivity it is often required when such small amount of sample are used.
The implementation of microflow LC–MS methods could result in sensitivity gain allowing an effective application of micro-sampling techniques.