Mass Spectrometry Letters

Korean Society for Mass Spectrometry (한국질량분석학회)
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Ultra-fast Generic LC-MS/MS Method for High-Throughput Quantification in Drug Discovery

  • Kim, So-Hee (Doping Control Center, Korea Institute of Science and Technology) ;
  • Yoo, Hye Hyun (Department of Pharmacy, College of Pharmacy, Hanyang University) ;
  • Cha, Eun-Ju (Doping Control Center, Korea Institute of Science and Technology) ;
  • Jeong, Eun Sook (Doping Control Center, Korea Institute of Science and Technology) ;
  • Kim, Ho Jun (Doping Control Center, Korea Institute of Science and Technology) ;
  • Kim, Dong Hyun (Department of Pharmacology and Pharmacogenomics Research Center, School of Medicine, Inje University) ;
  • Lee, Jaeick (Doping Control Center, Korea Institute of Science and Technology)
  • Received : 2013.08.29
  • Accepted : 2013.09.24
  • Published : 2013.09.30
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Abstract

An ultra-fast generic LC-MS/MS method was developed for high-throughput quantification of discovery pharmacokinetic (PK) samples and its reliability was verified. The method involves a simple protein precipitation for sample preparation and the analysis by ultra-fast generic LC-MS/MS with the ballistic gradient program and selected reaction monitoring (SRM) mode. Approximately 290 new chemical entities (NCEs) (over 10,000 samples) from 5 therapeutic programs were analyzed. The calibration curves showed good linearity in the concentration range of 1, 2 or 5 to 2000 ng/mL. No significant ion suppression was observed in the elution region of all the NCEs. When approximately 300 plasma samples were continuously analyzed, the peak area of internal standard was constant and reproducible. In the repeated analysis of samples, the plasma concentrations and the area under the curve (AUC) were consistent with the results from the first analysis. These results showed that the present ultra-fast generic LC-MS/MS method is reliable in terms of selectivity, sensitivity, and reproducibility and could be useful for high-throughput quantification and other bioanalysis in drug discovery.

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References

  1. Hoke, S. H.; Tomlinson, J. A.; Bolden, R. D.; Morand, K. L.; Pinkston, J. D.; Wehmeyer, K. R. Anal. Chem. 2001, 73, 3083. https://doi.org/10.1021/ac0014820
  2. Van Pelt, C. K.; Corso, T. N.; Schultz, G. A.; Lowes, S.; Henion, J. Anal. Chem. 2001, 73, 582. https://doi.org/10.1021/ac0006876
  3. Yang, L.; Mann, T. D.; Little, D.; Wu, N.; Clement, R. P.; Rudewicz, P. J. Anal. Chem. 2001, 73, 1740. https://doi.org/10.1021/ac0012694
  4. Yu, K.; Di, L.; Kerns, E.; Li, S. Q.; Alden, P.; Plumb, R. S. Rapid Commun. Mass Spectrom. 2007, 21, 893. https://doi.org/10.1002/rcm.2908
  5. Heinig, K.; Bucheli, F. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2003, 795, 337. https://doi.org/10.1016/S1570-0232(03)00603-2
  6. Yu, K.; Little, D.; Plumb, R.; Smith, B. Rapid Commun. Mass Spectrom. 2006, 20, 544. https://doi.org/10.1002/rcm.2336
  7. Kalovidouris, M.; Michalea, S.; Robola, N.; Koutsopoulou, M.; Panderi, I. Rapid Commun. Mass Spectrom. 2006, 20, 2939. https://doi.org/10.1002/rcm.2693
  8. Mallett, D. N.; Ramirez-Molina, C. J. Pharm. Biomed. Anal. 2009, 49, 100. https://doi.org/10.1016/j.jpba.2008.09.041
  9. Hsieh, Y.; Wang, G.; Wang, Y.; Chackalamannil, S.; Brisson, J. M.; Ng, K.; Korfmacher, W. A. Rapid Commun. Mass Spectrom. 2002, 16, 944. https://doi.org/10.1002/rcm.648
  10. Hsieh, Y.; Duncan, C. J.; Brisson, J. M. Anal. Chem. 2007, 79, 5668. https://doi.org/10.1021/ac070343g
  11. Cunliffe, J. M.; Maloney, T. D. J. Sep. Sci. 2007, 30, 3104. https://doi.org/10.1002/jssc.200700260
  12. Song, W.; Pabbisetty, D.; Groeber, E. A.; Steenwyk, R. C.; Fast, D. M. J. Pharm. Biomed. Anal. 2009, 50, 491. https://doi.org/10.1016/j.jpba.2009.05.011
  13. Badman, E. R.; Beardsley, R. L.; Liang, Z.; Bansal, S. J. Chromatogr. B Analyt. Technol. Biomed. Life Sci. 2010, 878, 2307. https://doi.org/10.1016/j.jchromb.2010.06.032
  14. Dunn-Meynell, K. W.; Wainhaus, S.; Korfmacher, W. A.; Rapid Commun. Mass Spectrom. 2005, 19, 2905. https://doi.org/10.1002/rcm.2147

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