The 2014 8th Workshop on Recent Issues in Bioanalysis (8th WRIB), a 5-day full immersion in the evolving field of bioanalysis, took place in Universal City, California, USA. Close to 500 professionals from pharmaceutical and biopharmaceutical companies, contract research organizations and regulatory agencies worldwide convened to share, review, discuss and agree on approaches to address current issues of interest in bioanalysis. The topics covered included both small and large molecules, and involved LCMS, hybrid LBA/LCMS, LBA approaches and immunogenicity. From the prolific discussions held during the workshop, specific recommendations are presented in this 2014 White Paper. As with the previous years' editions, this paper acts as a practical tool to help the bioanalytical community continue advances in scientific excellence, improved quality and better regulatory compliance. Due to its length, the 2014 edition of this comprehensive White Paper has been divided into three parts for editorial reasons. This publication (Part 2) covers the recommendations for Hybrid LBA/LCMS, Electronic Laboratory Notebook and Regulatory Agencies' Input. Part 1 (Small molecules bioanalysis using LCMS) was published in the Bioanalysis issue 6(22) and Part 3 (Large molecules bioanalysis using LBA and Immunogenicity) will be published in the Bioanalysis issue 6(24).
Background: Dapagliflozin is an inhibitor of sodium-glucose co-transporter 2 (SGLT-2) in development for the treatment of Type 2 diabetes. To support toxicology studies, LC–MS/MS methods were developed and validated for the quantitation of dapagliflozin in rat plasma. Results: The assay uses solid phase extraction and LC–MS/MS analysis in negative ion electrospray ionization mode. Because dapagliflozin readily forms adducts in the presence of formic acid, the mobile phases were simple mixtures of water and acetonitrile. The assay was validated in the concentration range of 5–2000 ng/ml with good intra- and inter-day precisions and acceptable sample stability. Conclusion: The validated assay was successfully applied to the quantitation of dapagliflozin in plasma in support of preclinical studies in both normal and diabetic rats.
