Application of A Tiered Approach to The Validation of Accelerator MS Assays

Abstract

Since its introduction into the drug-development arena, accelerator mass spectrometry (coupled with liquid chromatography fractionation) has been used to support a variety of study types. The uses to which the technique has been put include parent and/or metabolite quantification in pharmacokinetic studies, total radioactivity measurement in adsorption, metabolism and excretion studies, and quantitative metabolite profiling. A tiered approach has been applied to the verification of accelerator mass spectrometry assays, dependant on in which type of study and at what stage of drug development they are used. As accelerator mass spectrometry is an absolute detector that can quantify without the use of analyte-related standards, the specific assay verification requirements differ from those for LC–MS/MS assays. This article describes when screening, qualified and validated assay verification procedures should be applied, and suggests what parameters should be assessed in each case.

Financial & competing interests disclosure

The authors are or were employees of, and MS holds stock options in, Xceleron Inc., a company offering accelerator MS-enabled bioanalytical services on a commercial basis. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.