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Mass Balance by AMS Services

Administration of a 14C microtracer drug dose compounded with a full therapeutic mass dose of “cold” drug can provide definitive clinical mass balance and metabolism data earlier in the development cycle.

Traditional high 14C dose studies (macrotracer dose studies) typically require human dosimetry data and GMP manufactured 14C API.  We can accelerate timelines whenever the dose of 14C-drug is sufficiently low enough to preclude the need for human dosimetry or GMP 14C-API.

Our partners typically employ the 14C microtracer approach for human AME when presented with radiological safety concerns or specific PK criteria in addition to using the low radioactive dose approach for human metabolism purely for strategic reasons, either to expedite or reduce cost or both.

Sample preparation before AMS

Criteria for the 14C Microtracer Approach

  • Drug has a long elimination half-life in human and/or is slowly excreted
  • Drug accumulates in sensitive tissues (e.g. melanin binding, accumulation in liver/kidney)
  • Drug forms a major metabolite with a longer elimination half-life than parent
  • The hAME study must be conducted in sensitive populations (e.g. patients)
  • 14C-API is unstable due to auto-radiolytic decay

Our Experts Can Assist With:

  • Clinical study designs for healthy or patient volunteer subjects
  • Formulation of 14C – API (drug substance) suitable for human administration (drug product)
  • Sample preparation for total radioactivity analysis, including fecal sample homogenization
  • Quantitation of total 14C by LSC and/or AMS in whole blood, plasma, urine, feces and other matrices (e.g. expired air, CSF, tissue biopsies)
  • Hybrid LSC analysis combined with AMS when LSC reaches LOQ, which is commonly employed for total radioactivity (TRA)
  • Metabolite quantification and identification
  • Biotransformation pathways