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Title: Use of Accelerator Mass Spectrometry in Human Health and Molecular Toxicology

Accelerator mass spectrometry (AMS) has been adopted as a powerful bioanalytical method for human studies in the areas of pharmacology and toxicology. The exquisite sensitivity (10–18 mol) of AMS has facilitated studies of toxins and drugs at environmentally and physiologically relevant concentrations in humans. Such studies include risk assessment of environmental toxicants, drug candidate selection, absolute bioavailability determination, and more recently, assessment of drug-target binding as a biomarker of response to chemotherapy. Combining AMS with complementary capabilities such as high performance liquid chromatography (HPLC) can maximize data within a single experiment and provide additional insight when assessing drugs and toxins, such as metabolic profiling. Recent advances in the AMS technology at Lawrence Livermore National Laboratory have allowed for direct coupling of AMS with complementary capabilities such as HPLC via a liquid sample moving wire interface, offering greater sensitivity compared to that of graphite-based analysis, therefore enabling the use of lower 14C and chemical doses, which are imperative for clinical testing. In conclusion, the aim of this review is to highlight the recent efforts in human studies using AMS, including technological advancements and discussion of the continued promise of AMS for innovative clinical based research.
Authors:
 [1] ;  [1] ;  [2] ;  [1] ;  [2] ;  [1]
  1. Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
  2. UC Davis Medical Center, Sacramento, CA (United States); Accelerated Medical Diagnostics Inc., Berkeley, CA (United States)
Publication Date:
Report Number(s):
LLNL-JRNL-696717
Journal ID: ISSN 0893-228X
Grant/Contract Number:
AC52-07NA27344; HHSN261201000133C; HHSN261201200048C; HHSN261201200084C
Type:
Accepted Manuscript
Journal Name:
Chemical Research in Toxicology
Additional Journal Information:
Journal Volume: 29; Journal Issue: 12; Journal ID: ISSN 0893-228X
Publisher:
American Chemical Society (ACS)
Research Org:
Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)
Sponsoring Org:
USDOE; National Institutes of Health (NIH)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES
OSTI Identifier:
1367988

Enright, Heather A., Malfatti, Michael A., Zimmermann, Maike, Ognibene, Ted, Henderson, Paul, and Turteltaub, Kenneth W.. Use of Accelerator Mass Spectrometry in Human Health and Molecular Toxicology. United States: N. p., Web. doi:10.1021/acs.chemrestox.6b00234.
Enright, Heather A., Malfatti, Michael A., Zimmermann, Maike, Ognibene, Ted, Henderson, Paul, & Turteltaub, Kenneth W.. Use of Accelerator Mass Spectrometry in Human Health and Molecular Toxicology. United States. doi:10.1021/acs.chemrestox.6b00234.
Enright, Heather A., Malfatti, Michael A., Zimmermann, Maike, Ognibene, Ted, Henderson, Paul, and Turteltaub, Kenneth W.. 2016. "Use of Accelerator Mass Spectrometry in Human Health and Molecular Toxicology". United States. doi:10.1021/acs.chemrestox.6b00234. https://www.osti.gov/servlets/purl/1367988.
@article{osti_1367988,
title = {Use of Accelerator Mass Spectrometry in Human Health and Molecular Toxicology},
author = {Enright, Heather A. and Malfatti, Michael A. and Zimmermann, Maike and Ognibene, Ted and Henderson, Paul and Turteltaub, Kenneth W.},
abstractNote = {Accelerator mass spectrometry (AMS) has been adopted as a powerful bioanalytical method for human studies in the areas of pharmacology and toxicology. The exquisite sensitivity (10–18 mol) of AMS has facilitated studies of toxins and drugs at environmentally and physiologically relevant concentrations in humans. Such studies include risk assessment of environmental toxicants, drug candidate selection, absolute bioavailability determination, and more recently, assessment of drug-target binding as a biomarker of response to chemotherapy. Combining AMS with complementary capabilities such as high performance liquid chromatography (HPLC) can maximize data within a single experiment and provide additional insight when assessing drugs and toxins, such as metabolic profiling. Recent advances in the AMS technology at Lawrence Livermore National Laboratory have allowed for direct coupling of AMS with complementary capabilities such as HPLC via a liquid sample moving wire interface, offering greater sensitivity compared to that of graphite-based analysis, therefore enabling the use of lower 14C and chemical doses, which are imperative for clinical testing. In conclusion, the aim of this review is to highlight the recent efforts in human studies using AMS, including technological advancements and discussion of the continued promise of AMS for innovative clinical based research.},
doi = {10.1021/acs.chemrestox.6b00234},
journal = {Chemical Research in Toxicology},
number = 12,
volume = 29,
place = {United States},
year = {2016},
month = {10}
}