Bioanalysis of Drug in Tissue: Current Status and Challenges

This review, co-authored by QPS’ VP of Non-Clinical Development, Zamas Lam, covers current thinking on the bioanalysis of drugs in tissues, as opposed to in liquid matrices such as plasma. Tissue analysis poses particular technical challenges, but is important for understanding the pharmacological and toxicological properties of new drug candidates because, compared with plasma levels, it may more directly reflect the presence of drugs and their metabolites at the site of action. At the same time, it can alert researchers to potentially toxic accumulations of drugs within the body.

“Bioanalysis of Drug in Tissue: Current Status and Challenges” is a comprehensive overview, addressing a wide array of issues pertaining to tissue bioanalysis. The authors describe methods and special considerations for collecting and preparing various types of tissue, as well as ways to extract the analytes and measure them using LC–MS/MS and other modern technologies. Potential pitfalls are discussed, such as the difficulty of properly homogenizing hard tissues like bone, and the matrix effect, whereby high levels of phospholipids from homogenized cell membranes can lead to faulty chromatography results.

Because decisions about which tissue sampling methods to use are tissue- and study-specific, this article outlines a fit-for-purpose, tiered approach to developing and qualifying/validating tissue sampling methods at the various stages of drug discovery and development, to meet both scientific and regulatory requirements. The authors suggest that, in future, determining the fate of a drug and/or its metabolites through tissue analysis is likely to become more and more important as a way to investigate the safety of drug candidates, beyond the standard safety analyses based on plasma concentrations.

Bioanalysis of Drug in Tissue: Current Status and Challenges

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