A Flexible LCMS Front End for High-Throughput Bioanalytical Analysis in GLP Environment

Katty Wan, Julie Zhou, Maria Metchkarova, Jill Polzin and Matt Rieser; Abbott, Abbott Park, IL 60064

Presented at the 16th Symposium on Pharmaceutical and Bioanalytical Analysis (PBA 2005)

Introduction High throughput approaches for the quantitative analysis of drugs and related substances in complex biological matrices are critical to successful drug discovery and development programs. In an effort to capture effi ciencies available through two existing technologies, a staggered parallel HPLC system was developed with LEAP autosampler (CTC HTS PAL) equipped with trio valves and four independent HPLC pumps. Parallel LC-MS analysis is achieved by offset dual stream analysis with a time delay to allow staggering of the MS acquisition times. The system is confi gured to carry out either of the two analytical modes: • Paralleled LC-MS analysis with or without guard column regeneration • Paralleled on-line SPE followed by LC-MS analysis Timing and triggering for injections, analytical pumps, loading/ washing pumps and data collection are controlled by the Cycle Composer software that runs custom macros. Switching between the two operational modes requires minimal re- plumbing. The system can also run either type of analysis in single stream mode. Two regulated clinical studies (conducted under GLP) were analyzed using the system and are presented as two examples. One study used the dual channel HPLC with guard column regeneration. The other used the dual channel on-line SPE.