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Optimizing an ultrafast generic high‐performance liquid chromatography/tandem mass spectrometry method for faster discovery pharmacokinetic sample throughput
Author(s) -
DunnMeynell Kimberly W.,
Wainhaus Samuel,
Korfmacher Walter A.
Publication year - 2005
Publication title -
rapid communications in mass spectrometry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.528
H-Index - 136
eISSN - 1097-0231
pISSN - 0951-4198
DOI - 10.1002/rcm.2147
Subject(s) - chemistry , chromatography , tandem , mass spectrometry , sample (material) , throughput , analytical chemistry (journal) , tandem mass spectrometry , high performance liquid chromatography , sample preparation , matrix (chemical analysis) , telecommunications , materials science , computer science , composite material , wireless
For higher throughput screening, where the number of new chemical entities (NCEs) to test is rapidly increasing, fast sample turnaround time is essential. In order to increase efficiency a generic high‐performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS) method, with a cycle time of 85 s (42 injections/h), was created. This was accomplished through the use of a 1‐min ballistic gradient and the optimization of the autosampler. The gradient was optimized by varying the organic mobile phase concentration and examining its ballistic characteristics with respect to matrix ion suppression and compound retention time. The autosampler time could be reduced by optimizing several parameters and by determining the source of most of the carryover in order to reduce the number of syringe and injector washes. Finally, the reliability of the new generic method is demonstrated by comparison of sample data with a standard 2‐min linear gradient method that showed that the data sets were well correlated. For plasma AUC (ng.h/mL) of 28 NCEs, the regression line had a slope of 0.92 and the R 2 was 0.929. The described method was found to be useful for both rat plasma and tissue samples. Copyright © 2005 John Wiley & Sons, Ltd.