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Xenobiotica
the fate of foreign compounds in biological systems
Volume 31, 2001 - Issue 8-9
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Research Article

Accelerator mass spectrometry (AMS): recent experience of its use in a clinical study and the potential future of the technique

G. Young Division of Bioanalysis and Drug Metabolism, Glaxo Wellcome Research and Development Ltd, Park Road, Ware SG12 ODP, UK
,
W. Ellis Division of Bioanalysis and Drug Metabolism, Glaxo Wellcome Research and Development Ltd, Park Road, Ware SG12 ODP, UK
,
J. Ayrton Division of Bioanalysis and Drug Metabolism, Glaxo Wellcome Research and Development Ltd, Park Road, Ware SG12 ODP, UK
,
E. Hussey Division of Bioanalysis and Drug Metabolism, Glaxo Wellcome Research and Development Ltd, Park Road, Ware SG12 ODP, UK
&
B. Adamkiewicz Division of Bioanalysis and Drug Metabolism, Glaxo Wellcome Research and Development Ltd, Park Road, Ware SG12 ODP, UK
Pages 619-632 | Published online: 22 Sep 2008

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Graham Lappin & Lloyd Stevens. (2008) Biomedical accelerator mass spectrometry: recent applications in metabolism and pharmacokinetics. Expert Opinion on Drug Metabolism & Toxicology 4:8, pages 1021-1033.
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Sarah J. Roffey, R. Scott Obach, Jenny I. Gedge & Dennis A. Smith. (2007) What is the Objective of the Mass Balance Study? A Retrospective Analysis of Data in Animal and Human Excretion Studies Employing Radiolabeled Drugs. Drug Metabolism Reviews 39:1, pages 17-43.
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Articles from other publishers (52)

Tal Burt, Graeme Young, Wooin Lee, Hiroyuki Kusuhara, Oliver Langer, Malcolm Rowland & Yuichi Sugiyama. (2020) Phase 0/microdosing approaches: time for mainstream application in drug development?. Nature Reviews Drug Discovery 19:11, pages 801-818.
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Graeme C. Young & Marie Croft. 2020. Identification and Quantification of Drugs, Metabolites, Drug Metabolizing Enzymes, and Transporters. Identification and Quantification of Drugs, Metabolites, Drug Metabolizing Enzymes, and Transporters 185 210 .
Tal Burt & Robert D. Combes. 2019. The History of Alternative Test Methods in Toxicology. The History of Alternative Test Methods in Toxicology 229 240 .
Frédéric Lozac'h, Simon Fahrni, Daniele De Maria, Caroline Welte, Joël Bourquin, Hans-Arno Synal, David Pearson, Markus Walles & Gian Camenisch. (2018) Evaluation of cAMS for 14 C microtracer ADME studies: opportunities to change the current drug development paradigm . Bioanalysis 10:5, pages 321-339.
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Gordon J. Dear & Andrew McEwen. 2016. Metabolite Safety in Drug Development. Metabolite Safety in Drug Development 45 85 .
Graeme C Young & Mark Seymour. (2015) Application of 14 C-Accelerator MS in pharmaceutical development . Bioanalysis 7:5, pages 513-517.
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Angus N.R. Nedderman & Mark E. Savage. 2014. Handbook of Metabolic Pathways of Xenobiotics. Handbook of Metabolic Pathways of Xenobiotics 1 27 .
Takeshi KOBAYASHI, Teiko TOYOGUCHI, Kazuhiro KATO, Fuyuki TOKANAI & Tadashi SHIRAISHI. (2013) Quantitation of <sup>14</sup>C-Oxaliplatin Concentrations in Human Serum Samples by Using Accelerator Mass Spectrometry. RADIOISOTOPES 62:8, pages 517-523.
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David Higton, Graeme Young, Philip TimmermanRichard Abbott, Magnus Knutsson & Leif D Svensson. (2012) European Bioanalysis Forum recommendation: scientific validation of quantification by accelerator mass spectrometry. Bioanalysis 4:22, pages 2669-2679.
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Wing Wah Lam, Jose Silva & Heng‐Keang Lim. 2012. ADME‐Enabling Technologies in Drug Design and Development. ADME‐Enabling Technologies in Drug Design and Development 339 351 .
Marie Croft, Brendan Keely, Ian Morris, Lan Tann & Graham Lappin. (2012) Predicting Drug Candidate Victims of Drug-Drug Interactions, using Microdosing. Clinical Pharmacokinetics 51:4, pages 237-246.
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Graham LappinMark Seymour, Gerhard Gross, Martin Jørgensen, Morten Kall & Lisbet Kværnø. (2012) Meeting the MIST regulations: human metabolism in Phase I using AMS and a tiered bioanalytical approach. Bioanalysis 4:4, pages 407-416.
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Mark A Seymour. (2011) Accelerator MS: its role as a frontline bioanalytical technique. Bioanalysis 3:24, pages 2817-2823.
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Angus Nedderman. (2011) The use of accelerator MS in support of MIST. Bioanalysis 3:24, pages 2695-2699.
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Soo Kyung Bae & Ji-Hong Shon. (2011) Microdosing studies using accelerated mass spectrometry as exploratory investigational new drug trials. Archives of Pharmacal Research 34:11, pages 1789-1798.
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Lan Gao, Jing Li, Claudia Kasserra, Qi Song, Ali Arjomand, David Hesk & Swapan K Chowdhury. (2011) Precision and Accuracy in the Quantitative Analysis of Biological Samples by Accelerator Mass Spectrometry: Application in Microdose Absolute Bioavailability Studies. Analytical Chemistry 83:14, pages 5607-5616.
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Yoshiyuki Minamide, Yukio Osawa, Hiroshi Nishida, Harue Igarashi & Shinobu Kudoh. (2011) A highly sensitive LC-MS/MS method capable of simultaneously quantitating celiprolol and atenolol in human plasma for a cassette cold-microdosing study. Journal of Separation Science 34:13, pages 1590-1598.
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Jing-Tao Wu. 2011. Mass Spectrometry in Drug Metabolism and Disposition. Mass Spectrometry in Drug Metabolism and Disposition 567 578 .
Graham Lappin, Mark Seymour, Graeme Young, David Higton & Howard M Hill. (2011) AMS method validation for quantitation in pharmacokinetic studies with concomitant extravascular and intravenous administration. Bioanalysis 3:4, pages 393-405.
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Angus N. R. Nedderman & Don K. Walker. 2011. Pharmacokinetics in Drug Development. Pharmacokinetics in Drug Development 131 143 .
Fumin Li, John P. Zulkoski, Jie Ding, Wes Brown & Tom Addison. (2010) Liquid chromatography/tandem mass spectrometry sensitivity enhancement via online sample dilution and trapping: applications in microdosing and dried blood spot (DBS) bioanalysis. Rapid Communications in Mass Spectrometry 24:17, pages 2575-2583.
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Stephen R DuekerPeter N LohstrohJason A GiacomoLe T VuongBradly D KeckJohn S Vogel. (2010) Early human ADME using microdoses and microtracers: bioanalytical considerations. Bioanalysis 2:3, pages 441-454.
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M Simpson, G LappinBJ Keely. (2010) Development of 2D chiral chromatography with accelerator mass spectrometry for quantification of 14 C-labeled R - and S -verapamil in plasma . Bioanalysis 2:3, pages 397-405.
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Ali Arjomand. (2010) Accelerator mass spectrometry-enabled studies: current status and future prospects. Bioanalysis 2:3, pages 519-541.
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Lan Gao & Swapan Chowdhury. 2009. Using Mass Spectrometry for Drug Metabolism Studies, Second Edition. Using Mass Spectrometry for Drug Metabolism Studies, Second Edition 391 418 .
Don Walker, Joe Brady, Deepak Dalvie, John Davis, Martin Dowty, J. Neil Duncan, Angus Nedderman, R. Scott Obach & Pat Wright. (2009) A Holistic Strategy for Characterizing the Safety of Metabolites through Drug Discovery and Development. Chemical Research in Toxicology 22:10, pages 1653-1662.
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Angus N. R. Nedderman. (2009) Metabolites in safety testing: metabolite identification strategies in discovery and development. Biopharmaceutics & Drug Disposition 30:4, pages 153-162.
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S. Nilgün Çömezoğlu, Van T. Ly, Donglu Zhang, W. Griffith Humphreys, Samuel J. Bonacorsi, Donald W. Everett, Marvin B. Cohen, Jinping Gan, Jan H. Beumer, Jos H. Beijnen, Jan H.M. Schellens & Graham Lappin. (2009) Biotransformation Profiling of [14C]Ixabepilone in Human Plasma, Urine and Feces Samples Using Accelerator Mass Spectrometry (AMS). Drug Metabolism and Pharmacokinetics 24:6, pages 511-522.
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Yoshihiro Miyaji, Tomoko Ishizuka, Kenji Kawai, Yoshimi Hamabe, Teiji Miyaoka, Toshinari Oh-hara, Toshihiko Ikeda & Atsushi Kurihara. (2009) Use of An Intravenous Microdose of 14C-labeled drug and Accelerator Mass Spectrometry to measure Absolute Oral Bioavailability in Dogs; Cross-comparison of Assay Methods by Accelerator Mass Spectrometry and Liquid Chromatography-Tandem Mass Spectrometry. Drug Metabolism and Pharmacokinetics 24:2, pages 130-138.
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G. C. Young, S. Corless, C. C. Felgate & P. V. Colthup. (2008) Comparison of a 250 kV single-stage accelerator mass spectrometer with a 5 MV tandem accelerator mass spectrometer - fitness for purpose in bioanalysis. Rapid Communications in Mass Spectrometry 22:24, pages 4035-4042.
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Wing W. Lam, Cho‐Ming Loi, Angus Nedderman & Don Walker. 2008. Mass Spectrometry in Drug Metabolism and Pharmacokinetics. Mass Spectrometry in Drug Metabolism and Pharmacokinetics 253 273 .
Ryogo Minamimoto, Yoshimi Hamabe, Teiji Miyaoka, Takamitsu Hara, Keisuke Yoshida, Takashi Oka & Tomio Inoue. (2009) Accelerator mass spectrometry analysis of background 14C-concentrations in human blood: aiming at reference data for further microdosing studies. Annals of Nuclear Medicine 22:10, pages 883-889.
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Alan V. Boddy, Julieann Sludden, Melanie J. Griffin, Colin Garner, John Kendrick, Pritesh Mistry, Catherine Dutreix, David R. Newell & Stephen G. O'Brien. (2007) Pharmacokinetic Investigation of Imatinib Using Accelerator Mass Spectrometry in Patients with Chronic Myeloid Leukemia. Clinical Cancer Research 13:14, pages 4164-4169.
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G.C. Young & W.J. Ellis. (2007) AMS in drug development at GSK. Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms 259:1, pages 752-757.
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Graham Lappin. 2006. Radiotracers in Drug Development. Radiotracers in Drug Development 233 249 .
Suresh K. Balani, Nelamangala V. Nagaraja, Mark G. Qian, Arnaldo O. Costa, J. Scott Daniels, Hua Yang, Prakash R. Shimoga, Jing-Tao Wu, Liang-Shang Gan, Frank W. Lee & Gerald T. Miwa. (2006) EVALUATION OF MICRODOSING TO ASSESS PHARMACOKINETIC LINEARITY IN RATS USING LIQUID CHROMATOGRAPHY-TANDEM MASS SPECTROMETRY. Drug Metabolism and Disposition 34:3, pages 384-388.
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Karen Brown, Elaine M. Tompkins & Ian N.H. White. (2006) Applications of accelerator mass spectrometry for pharmacological and toxicological research. Mass Spectrometry Reviews 25:1, pages 127-145.
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Ulrich Pleiss. (2005) Radioaktiv markierte pharmazeutische Wirkstoffe: Werkzeuge bei der Arzneimittelentwicklung. Pharmazie in unserer Zeit 34:6, pages 514-519.
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Nenad Sarapa, Poe-Hirr Hsyu, Graham Lappin & Ronald Colin Garner. (2005) The Application of Accelerator Mass Spectrometry to Absolute Bioavailability Studies in Humans: Simultaneous Administration of an Intravenous Microdose of 14 C-Nelfinavir Mesylate Solution and Oral Nelfinavir to Healthy Volunteers . The Journal of Clinical Pharmacology 45:10, pages 1198-1205.
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Sandra Coecke, Bas J. Blaauboer, Greetje Elaut, Stuart Freeman, Andreas Freidig, Nigel Gensmantel, Peter Hoet, Vassilios M. Kapoulas, Bernhard Ladstetter, Gill Langley, David Leahy, Geert Mannens, Annarita Meneguz, Mario Monshouwer, Ben Nemery, Olavi Pelkonen, Walter Pfaller, Pilar Prieto, Nick Proctor, Vera Rogiers, Amin Rostami-Hodjegan, Enrico Sabbioni, Winfried Steiling & Johannes J.M. van de Sandt. (2019) 3.9. Toxicokinetics and Metabolism. Alternatives to Laboratory Animals 33:1_suppl, pages 147-175.
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Emma Janet Castillo, Silvia Delgado-Aros, Michael Camilleri, Duane Burton, Debra Stephens, Robin O'Connor-Semmes, Ann Walker, Anne Shachoy-Clark & Alan R. Zinsmeister. (2004) Effect of oral CCK-1 agonist GI181771X on fasting and postprandial gastric functions in healthy volunteers. American Journal of Physiology-Gastrointestinal and Liver Physiology 287:2, pages G363-G369.
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Graham Lappin & R. Colin Garner. (2003) Big physics, small doses: the use of AMS and PET in human microdosing of development drugs. Nature Reviews Drug Discovery 2:3, pages 233-240.
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Graham Lappin & R. Colin Garner. 2003. Bioanalytical Separations. Bioanalytical Separations 331 349 .
R. C. Garner, I. Goris, A. A. E. Laenen, E. Vanhoutte, W. Meuldermans, S. Gregory, J. V. Garner, D. Leong, M. Whattam, A. Calam & C. A. W. Snel. (2002) Evaluation of Accelerator Mass Spectrometry in a Human Mass Balance and Pharmacokinetic Study–Experience with 14 C-labeled ( R )-6-[Amino(4- chlorophenyl)(1-methyl-1 H -imidazol-5-yl)methyl]-4-(3-chlorophenyl)-1- methyl-2(1 H )-quinolinone (R115777), a Farnesyl Transferase Inhibitor . Drug Metabolism and Disposition 30:7, pages 823-830.
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