Metabolites in Safety Testing

Ragu Ramanathan, Dil M. Ramanathan

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

This chapter summarizes the current thinking and practices in the pharmaceutical industry in support of metabolites in safety testing (MIST) related activities. It compares two of several options available for conducting absorption, distribution, metabolism, and excretion (ADME) studies using radiolabled materials. In the first option, radiolabeled studies are not scheduled until after the interpretation of human pharmacokinetics (PK) and metabolism in the first-in-human (FIH) studies, while in the second option, preclinical radiolabeled ADME studies are initiated before the completion of the FIH studies. The chapter discusses some of the liquid chromatography-mass spectrometry (LC-MS) methods available for detecting and characterizing metabolites. Bioanalytical assays, used for detection, characterization and exposure estimation of metabolites, are tiered into (i) metabolite profiling, (ii) standard free quantification/ response factor determination, (iii) qualified assays, and (vi) validated assays.

Original languageEnglish
Title of host publicationHandbook of LC-MS Bioanalysis
Subtitle of host publicationBest Practices, Experimental Protocols, and Regulations
Publisherwiley
Pages71-82
Number of pages12
ISBN (Electronic)9781118671276
ISBN (Print)9781118159248
DOIs
StatePublished - 30 Aug 2013

Keywords

  • Absorption, distribution, metabolism, and excretion (ADME)
  • Disproportionate human metabolite
  • First-in-human (FIH) studies
  • Human specific metabolite, metabolites in safety testing (MIST)
  • Radiolabeled materials
  • Tiered assays

Fingerprint

Dive into the research topics of 'Metabolites in Safety Testing'. Together they form a unique fingerprint.

Cite this