Bioanalytics – Chemical
LC-MS/MS has been used for large and small molecule bioanalysis to support PK and TK analyses. LC-MS technology and its application to support biomarker analysis in clinical trials is still at its early stage. Lack of full understanding of the technology and many technical/regulatory challenges still prevent the community from using the technology to its full potential in drug development and personalized medicine applications. From both an instrumental and experimental perspective, LC-MS quantification of biomarkers in biological fluids shares many similarities to drug candidate bioanalysis. Key differences include the presence of target analyte(s) in the control matrices used to prepare calibrator and QC samples and greater difficulty in procuring characterized working standards. AAPS Bioanalysis Focus Group, AAPS Bioanalysis Ligand Binding Assay Focus Group and AAPS Biomarker in Translational Medicine Focus Group (recently joined as the Biomarker and Precision Medicine Community) formed several sub committees to review the technology, regulatory requirements and its applications and prepared two white papers on this topic. This presentation will deliver the recommendations from one subcommittee regarding LC/MS-based biomarker validation for both small and large molecules. The recommendations made in this white paper reflect extensive discussions undertaken by the authors as part of the AAPS Bioanalytical Focus Group and pertain specifically to practices undertaken during pharmaceutical research and development.