LC-ICP-MS: A maturing bioanalytical alternative for metabolite profiling and mass-balance studies

Understanding the metabolism of the drug candidate has important implications for drug discovery and development. Biotransformation—changing drugs into less toxic, less active forms that are excretable in urine—is essential but can have negative effects, such as rapid clearance or the formation of active or reactive or other toxic metabolites. The metabolic fate of drugs usually has been studied during early phases of research and development using quick in vitro approaches. In this white paper, Xendo Drug Development Services describes an alternative metabolic profiling technique that makes use of liquid chromatography (LC), inductively coupled plasma (ICP) and mass spectrometry (MS). This technique was found to be excellent in the absence of authentic standards and, because the technique is not dependent on radiolabeled substances, potentially hazardous clinical studies are avoided.

Metabolic profiling of new compounds includes detection of metabolites, structure characterization and quantitative analysis. When the concentrations of metabolites are extremely low and highly specific, sensistive analytical methods are required. LC/MS is a widely used method. LC-ICP-MS provides a sensitive, highly specific method for detecting atoms such as phosphorus, bromine, chlorine and sulfur. Although LC-ICP-MS has been used mainly for metals or metal-containing drugs, it offers the ability to monitor elements and can be of value in other areas of pharmacology.

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