Carbon-14 Microtracers Services
Carbon-14 (14C) microtracers are defined as the administration of a small tracer dose of carbon-14 (14C) in combination with a therapeutic, pharmacologically relevant mass dose of the drug.
We employ the exquisite sensitivity of AMS as the analytical platform to support the quantification of [14C] in all biological matrices of interest. Typically for human AME studies, the radioactivity administered is in the range of 1-5 µCi per subject, and at these levels, human dosimetry data is not normally required.
Pharmaron integrates the radiosynthesis and purification of 14C radiolabelled compounds with the conduct of non-clinical ADME and QWBA studies followed by the conduct of the definitive Phase I hAME clinical study. By combining 14C microtracers with ultra-sensitive 14C-AMS detection, we can help accelerate your clinical program and de-risk your compound as it enters Phase II/III clinical trials.
AMS-enabled 14C Microtracer Approaches
- Non-GMP 14C drug substance employing clinical-grade purified 14C-API in the 14C drug product
- Phase l human AME (microtracer) under open IND
- Exploratory Phase 0 (microdose) under eIND (exploratory IND)
- 14C IV microtracers for intravenous PK and absolute bioavailability
- Mass balance using AMS or hybrid LSC + AMS to determine total radioactivity in blood, plasma, and excreta
- Metabolite profiling by LC+AMS (ultra-high resolution metabolite profiles critical for drugs with complex metabolism)
- Metabolite ID (MetID) by HRMS
- 14C-AMS is used for both small molecules and biologics
Microtracer vs Microdose Definitions
- Microtracer is a radioactive dose (typically <5 µCi) utilizing a low mass dose of the 14C-drug compounded with the GMP “cold” drug at the prescribed therapeutic dose. Microtracer studies are, therefore, conducted at a full therapeutic dose labelled with 14C employing AMS analysis.
- Microdose is a mass dose equivalent to ≤100 µg or ≤1/100th of the pharmacological active dose (whichever is the lower per FDA guidelines). Microdose studies are, therefore, conducted at a sub-therapeutic dose labelled with either 13C or 14C utilizing either LC-MS/MS or AMS analysis respectively.