High sensitivity laboratory based 14C analysis for drug discovery

Erhan Ilkmen, D. E. Murnick

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

An ultra-sensitive laser-based analytical technique, intracavity optogalvanic spectroscopy (ICOGS) providing extremely high sensitivity for detection of 14C-labeled carbon dioxide has been demonstrated. Obviating the need for scintillation counting and capable of replacing accelerator mass spectrometers (AMS), the technique can quantify zeptomoles of 14C in sub-micromole CO2 samples. Based on the specificity of laser resonances, coupled with the sensitivity provided by standing waves in an optical cavity, and detection via impedance variations, limits of detection near 10-15 14C/12C ratios have been obtained. With the use of a 15 Watt 14CO2 laser, a linear calibration with samples from ≈10-15 to ≈10-11 in 14C/12C ratios was demonstrated. Calibrations become nonlinear over larger concentration ranges due to laser and ICOGS saturation effects and changes in equilibration time constants. Conditions, however, can be chosen to provide near linear response over different dynamic ranges. Drug discovery applications such as radiolabeling studies with extremely low specific activity, microdosing studies, and individualized sub therapeutic tests of drug metabolism typically involve samples having 14C/12C ratios in the approximate range of 1 to 100 × 10-12. A laboratory instrument for that range will be small (table top), low maintenance and capable of being interfaced to GC or LC inputs.

Original languageEnglish (US)
Pages (from-to)304-307
Number of pages4
JournalJournal of Labelled Compounds and Radiopharmaceuticals
Volume53
Issue number5-6
DOIs
StatePublished - May 1 2010

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Drug Discovery
Lasers
Calibration
Spectrum Analysis
Spectroscopy
Scintillation Counting
Scintillation
Mass spectrometers
Electric Impedance
Metabolism
Carbon Dioxide
Particle accelerators
Limit of Detection
Maintenance
Pharmaceutical Preparations
Therapeutics

All Science Journal Classification (ASJC) codes

  • Analytical Chemistry
  • Biochemistry
  • Radiology Nuclear Medicine and imaging
  • Drug Discovery
  • Spectroscopy
  • Organic Chemistry

Keywords

  • C
  • Carbon isotopes
  • Drug discovery
  • Microdose
  • Optogalvanic spectroscopy
  • Radiocarbon

Cite this

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title = "High sensitivity laboratory based 14C analysis for drug discovery",
abstract = "An ultra-sensitive laser-based analytical technique, intracavity optogalvanic spectroscopy (ICOGS) providing extremely high sensitivity for detection of 14C-labeled carbon dioxide has been demonstrated. Obviating the need for scintillation counting and capable of replacing accelerator mass spectrometers (AMS), the technique can quantify zeptomoles of 14C in sub-micromole CO2 samples. Based on the specificity of laser resonances, coupled with the sensitivity provided by standing waves in an optical cavity, and detection via impedance variations, limits of detection near 10-15 14C/12C ratios have been obtained. With the use of a 15 Watt 14CO2 laser, a linear calibration with samples from ≈10-15 to ≈10-11 in 14C/12C ratios was demonstrated. Calibrations become nonlinear over larger concentration ranges due to laser and ICOGS saturation effects and changes in equilibration time constants. Conditions, however, can be chosen to provide near linear response over different dynamic ranges. Drug discovery applications such as radiolabeling studies with extremely low specific activity, microdosing studies, and individualized sub therapeutic tests of drug metabolism typically involve samples having 14C/12C ratios in the approximate range of 1 to 100 × 10-12. A laboratory instrument for that range will be small (table top), low maintenance and capable of being interfaced to GC or LC inputs.",
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High sensitivity laboratory based 14C analysis for drug discovery. / Ilkmen, Erhan; Murnick, D. E.

In: Journal of Labelled Compounds and Radiopharmaceuticals, Vol. 53, No. 5-6, 01.05.2010, p. 304-307.

Research output: Contribution to journalArticle

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AB - An ultra-sensitive laser-based analytical technique, intracavity optogalvanic spectroscopy (ICOGS) providing extremely high sensitivity for detection of 14C-labeled carbon dioxide has been demonstrated. Obviating the need for scintillation counting and capable of replacing accelerator mass spectrometers (AMS), the technique can quantify zeptomoles of 14C in sub-micromole CO2 samples. Based on the specificity of laser resonances, coupled with the sensitivity provided by standing waves in an optical cavity, and detection via impedance variations, limits of detection near 10-15 14C/12C ratios have been obtained. With the use of a 15 Watt 14CO2 laser, a linear calibration with samples from ≈10-15 to ≈10-11 in 14C/12C ratios was demonstrated. Calibrations become nonlinear over larger concentration ranges due to laser and ICOGS saturation effects and changes in equilibration time constants. Conditions, however, can be chosen to provide near linear response over different dynamic ranges. Drug discovery applications such as radiolabeling studies with extremely low specific activity, microdosing studies, and individualized sub therapeutic tests of drug metabolism typically involve samples having 14C/12C ratios in the approximate range of 1 to 100 × 10-12. A laboratory instrument for that range will be small (table top), low maintenance and capable of being interfaced to GC or LC inputs.

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