A High-Capacity LC/MS System for the Bioanalysis of Samples Generated from Plate-Based Metabolic Screening

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• 作者：John S. Janiszewski ; Katrina J. Rogers ; Kevin M. Whalen ; Mark J. Cole ; Theodore E. Liston ; Eva Duchoslav ; and Hassan G. Fouda
• 刊名：Analytical Chemistry
• 出版年：2001
• 出版时间：April 1, 2001
• 年：2001
• 卷：73
• 期：7
• 页码：1495 - 1501
• 全文大小：219K
• 年卷期：v.73,no.7(April 1, 2001)
• ISSN：1520-6882

文摘

HPLC/MS is a linear technique characterized by serialinjection and analysis of individual samples. Parallel-format high-throughput screens for druglike propertiespresent a significant analytical challenge. Analysis speedand system ruggedness are key requirements for bioanalysis of thousands of samples per day. The tasksinvolved in LC/MS analysis are readily divided into threeareas, sample preparation/liquid handling, LC/MS methodbuilding/sample analysis, and data processing. Severalautomation and multitasking strategies were developedand implemented to minimize plating and liquid handlingerrors, reduce dead times within the analysis cycle, andallow for comprehensive review of data. Delivering multiple samples to multiple injectors allows the autosamplertime to complete its wash cycles and aspirate the next setof samples while the previous set is being analyzed. Adual-column chromatography system provides columncycling and peak stacking and allows rapid throughputusing conventional LC equipment. Collecting all data fora compound into a single file greatly reduces the numberof data files collected, increases the speed of data collection, allows rugged and complete review of all data, andprovides facile data management. The described systemshave analyzed over 40 000 samples per month for twoyears and have the capacity for over 2000 samples perinstrument per day.