Bioanalysis works in the IAA AMS facility: Comparison of AMS analytical method with LSC method in human mass balance study

Miyaoka, Teiji; Isono, Yoshimi; Setani, Kaoru; Sakai, Kumiko; Yamada, Itsunari; Sato, Yoshiaki; Gunji, Shinobu; Matsui, Teruo

doi:10.1016/j.nimb.2007.02.001

Cited by 17 publications

(13 citation statements)

References 2 publications

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“…The AMS system is a highly sensitive analysis method that can be used for measuring radiocarbon concentrations ( 14 C/ 12 C ratio). The sensitivity of AMS is more than 1000 times higher than that of the conventional beta ray counting methods such as an LSC [5]. AMS has been applied to the fi elds of archeology, geology, and environmental and earth sciences.…”

Section: Introductionmentioning

confidence: 99%

“…During the early stages of drug development, administration of compounds with low radioactivity in humans is possible when using highly sensitive analyzers such as AMS or PET. Application of AMS or PET in bioanalytical studies has earlier been used and is expected to become the principal method for such bioanalysis approaches in the future [5]. We used the AMS system to measure the background 14 Cconcentration in human blood for the purpose of evaluating its potential use as a reference in microdose studies that administer 14 C-labeled compounds in humans.…”

Section: Introductionmentioning

confidence: 99%

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Accelerator mass spectrometry analysis of background 14C-concentrations in human blood: aiming at reference data for further microdosing studies

Minamimoto

Hamabe²,

Miyaoka³

et al. 2008

Ann Nucl Med

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Accelerator mass spectrometry analysis of background 14C-concentrations in human blood: aiming at reference data for further microdosing studies

Minamimoto

Hamabe²,

Miyaoka³

et al. 2008

Ann Nucl Med

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“…13 After measurements of protein contents and radioactivities of the analyte spots, the covalent binding levels were calculated.…”

Section: Methodsmentioning

confidence: 99%

Zone analysis by two-dimensional electrophoresis with accelerator mass spectrometry of in vivo protein bindings of idiosyncratic hepatotoxicants troglitazone and flutamide bioactivated in chimeric mice with humanized liver

et al. 2015

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Analyses using electrophoresis with accelerator mass spectrometry revealed that in vivo bioactivated radiolabeled troglitazone and flutamide, both known to be hepatotoxic in humans, bound nonspecifically to a variety of microsomal and cytosolic proteins in livers from chimeric mice with humanized liver. Unlike those of radiolabeled diazepam (rarely hepatotoxic) and previously reported 5-n-butyl-pyrazolo[1,5-a]-pyrimidine (limited hepatotoxicity), some troglitazone and flutamide binding proteins were located in the top right area in a zone analysis, representing high covalent binding contents and high target protein concentrations. Among a variety of liver microsomal proteins bound, the binding target proteins of troglitazone and flutamide with the highest covalent binding contents (in terms of pmol equivalent per µg target protein) were 17β-hydroxysteroid dehydrogenase and 3β-hydroxysteroid dehydrogenase, respectively.Troglitazone and flutamide were activated to reactive metabolites and apparently bound to different target proteins in livers from chimeric mice with humanized liver. The highest covalent binding contents for troglitazone were higher than that for flutamide under the present conditions. These results indicate that the drug metabolism mediated by humanized livers (leading to binding in vivo) in combination with a zone analysis of covalent binding contents/target protein concentration data could be a good tool for evaluating the relationship between the nonspecific protein binding behavior of medicines and potential hepatotoxicity in humans. Thus, testing whether protein binding data of new medicines are unbalanced with respect to deviation from an inverse relationship or the presence of data points in the high covalent binding/high protein concentration zone might be an important concept in evaluating hepatotoxic potential.

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“…This enables radiolabel studies to be undertaken at in the nanoCurie range (Barker and Garner 1999), which is below the Department of Health's Administration of Radioactive Substances Advisory Committee limit for requiring approval, reducing the time taken to progress the compound to man. AMS correlates well with traditional liquid scintillation counting methods (Miyaoka et al 2007) and has been successfully applied to mass balance studies and metabolic profiling (Miyaoka et al 2007). The sensitivity of AMS is also a disadvantage in that extreme care must be taken in sample handling to avoid contamination (Buchholz et al 2000).…”

Section: Semi-quantitative Considerationsmentioning

confidence: 99%

Metabolite identification by mass spectrometry: forty years of evolution

Wright

2011

Xenobiotica

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When the Drug Metabolism Discussion Group was instigated in 1971, metabolite identification by mass spectrometry was a slow and laborious process undertaken by mass spectrometrists who seemed to continually disappoint their colleagues by failing to obtain the metabolite spectra. This was usually because not enough material was supplied or the material was impure. Today, accurate metabolite information can be obtained rapidly with little material by utilizing a range of mass spectrometers with complementary properties. This review will discuss how both technology and strategy have evolved over the past forty years to meet the changing demands of metabolism studies within the pharmaceutical industry.

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Bioanalysis works in the IAA AMS facility: Comparison of AMS analytical method with LSC method in human mass balance study

Cited by 17 publications

References 2 publications

Accelerator mass spectrometry analysis of background 14C-concentrations in human blood: aiming at reference data for further microdosing studies

Accelerator mass spectrometry analysis of background 14C-concentrations in human blood: aiming at reference data for further microdosing studies

Zone analysis by two-dimensional electrophoresis with accelerator mass spectrometry of in vivo protein bindings of idiosyncratic hepatotoxicants troglitazone and flutamide bioactivated in chimeric mice with humanized liver

Metabolite identification by mass spectrometry: forty years of evolution

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