RESUMEN
BACKGROUND: Automated methodologies using silica-based, monolithic, micropipette tip-based SPE have been developed for the analysis of small molecules in support of both preclinical and first-in-human development studies using LC-MS/MS. The use of micropipette tip-based SPE with the Tomtec Quadra 96(®) and the evaluation of prototype micropipette tips for use with the Hamilton Microlab(®) Star robot is outlined. RESULTS: Mixed-mode cation exchange and C18 SPE methods have been developed using human and rat plasma for the extraction of lipophilic and polar analytes. These methods are advantageous as they use low plasma sample, washing and elution volumes and result in a method extraction cycle time of approximately 6.2 min for 96 samples. CONCLUSION: This significantly reduced extraction time, compared with 96-well plate format SPE, indicates that the sample preparation stage is no longer the rate-limiting stage in performing a selective extraction procedure. Robust and sensitive methods have been developed that have proven to be more cost effective than traditional 96-well plate format SPE methods.