| High-throughput liquid chromatography/mass spectrometry method for the quantitation of small molecules using accurate mass technologies in supporting discovery drug screening. | |
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MedLine Citation:
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PMID: 23280971 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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RATIONALE: Drug discovery samples are routinely analyzed using liquid chromatography/tandem mass spectrometry (LC/MS/MS) methods on triple quadrupole mass spectrometers employing multiple reaction monitoring (MRM). In order to improve analysis throughput, quantitation of small molecules on a quadrupole time-of-flight (QqTOF) instrument using TOF scan and high-resolution MRM (MRM-HR) modes was evaluated in this study. METHODS: Cassette dosed plasma and brain samples from nine compounds were extracted using a protein precipitation method. Separation was achieved by reversed-phase liquid chromatography. Mass spectrometric analysis was performed using TOF scan and high-resolution MRM approaches on a QqTOF mass spectrometer with turbo-ionspray ionization. Results were compared to those obtained on a triple quadrupole mass spectrometer. RESULTS: The dynamic range varied depending on compounds and instruments and was similar between the MRM on QqQ and full TOF scan mode on QqTOF. Linear or quadratic regression and 1/x(2) weighting were used. Resolution on the QqTOF instrument was around 32000 and mass accuracy was within 4.4 ppm. The MRM-HR method showed better sensitivity compared to the TOF scan method, and was comparable to the MRM on a QqQ mass spectrometer. Assay accuracy was within ±25%. CONCLUSIONS: A TOF scan method allowed the use of the generic method without compound-specific optimization and was an alternative choice for routine high-throughput quantitation of small molecules. The MRM-HR method on the QqTOF showed good sensitivity which was comparable to that obtained by the MRM method on the triple quadrupole mass spectrometer. Copyright © 2012 John Wiley & Sons, Ltd. |
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Authors:
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Xiao Ding; Hesham Ghobarah; Xiaolin Zhang; Allan Jaochico; Xingrong Liu; Gauri Deshmukh; Bianca M Liederer; Cornelis E C A Hop; Brian Dean |
Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Rapid communications in mass spectrometry : RCM Volume: 27 ISSN: 1097-0231 ISO Abbreviation: Rapid Commun. Mass Spectrom. Publication Date: 2013 Feb |
Date Detail:
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Created Date: 2013-01-02 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8802365 Medline TA: Rapid Commun Mass Spectrom Country: England |
Other Details:
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Languages: eng Pagination: 401-8 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 John Wiley & Sons, Ltd. |
Affiliation:
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Genentech, Inc., Drug Metabolism and Pharmacokinetics, MS 412A, 1 DNA Way, South San Francisco, CA 94080, USA. ding.xiao@gene.com. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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