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  • P-ISSN 2233-4203
  • E-ISSN 2093-8950

Ultra-fast Generic LC-MS/MS Method for High-Throughput Quantification in Drug Discovery

Mass Spectrometry Letters / Mass Spectrometry Letters, (P)2233-4203; (E)2093-8950
2013, v.4 no.3, pp.47-50
https://doi.org/10.5478/MSL.2013.4.3.47
Kim So-Hee (Korea Institute of Science and Technology)
Yoo Hye Hyun (Hanyang University)
Cha Eun-Ju (Korea Institute of Science and Technology)
Jeong Eun Sook (Korea Institute of Science and Technology)
Kim Ho Jun (Korea Institute of Science and Technology)
Kim Dong Hyun (Inje University)
Lee Jaeick (Korea Institute of Science and Technology)
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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 preparationand 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 suppressionwas 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 concentrationsand the area under the curve (AUC) were consistent with the results from the first analysis. These results showed that the presentultra-fast generic LC-MS/MS method is reliable in terms of selectivity, sensitivity, and reproducibility and could be useful forhigh-throughput quantification and other bioanalysis in drug discovery.

keywords
LC-MS/MS, high-throughput quantification, drug discovery, ballistic gradient system


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Submission Date
2013-08-29
Revised Date
2013-09-24
Accepted Date
2013-09-24
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