Open access liquid chromatography/tandem mass spectrometry: implementation of a fully quantitative system in a drug discovery laboratory

John G Swales, Gary Wilkinson, Richard Gallagher, Clare Hammond, Charles O’Donnell, Raimund PeterAstraZeneca, Discovery Drug Metabolism and Pharmacokinetics, CVGI Research Area, Alderley Park, Macclesfield, Cheshire, UKAbstract: High performance liquid chromatography with electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) has been utilized to produce fully open access (OA) quantitative systems. The systems described have the ability to optimize the mass spectrometer analysis method, stack these optimizations, create the mass spectrometry analytical methods and automatically process data for reporting. An in-house, Microsoft Excel-based sample list generator in conjunction with two manufacturers’ OA software packages have been implemented and are used exclusively for all in vivo and in vitro drug metabolism and pharmacokinetic assays within the department. We demonstrate that the OA systems have had a positive effect on the average turnaround times of all assays by utilizing the mass spectrometer time more effectively and by minimizing instrument downtime. Turnaround times have been monitored for 17 months post implementation of the OA systems as part of a Lean Six Sigma efficiency optimization project, and data are presented that support a sustained improvement throughout this period.Keywords: open access, DMPK, quantitation, bioanalysis, discovery