Accelerator Mass Spectrometry - AMS Chemistry

Accelerator Mass Spectrometry (AMS)

Accelerator Mass Spectrometry (AMS) is an ultra sensitive analytical technique that detects and quantifies ¹⁴C atoms at trace levels that are 500 – 10,000 times more sensitive than traditional liquid scintillation counting (LSC) or LC-MS/MS methods. Originally used for radiocarbon dating, AMS was introduced for biomedical applications in the early 2000s and now plays a routine and pivotal role in pharmaceutical R&D. With no matrix interference or ionization issues, AMS is applicable to low-dose, long half-life and low systemic drug exposure analysis.

Utilizing AMS technology, a wide range of sample types can be analyzed, including standard matrices (e.g. plasma, whole blood, urine, faeces, etc), and additionally, more unusual matrices (e.g., bile, expired air traps, dialysate, tissue (tumor biopsies), CSF).

¹⁴C analysis by AMS for Clinical Metabolism and PK Studies

For over 25 years, Pharmaron has been a recognized leader in developing and utilizing AMS technology for clinical metabolism and PK studies. With world-class AMS facilities in the US, UK and China, our team primarily focuses on employing AMS as an ultra sensitive ¹⁴C analytical platform to support pharmaceutical and biopharmaceutical R&D. The advantages of AMS technology include ultra-sensitive LLOQs (sub-pg equivalents per mL), no matrix interference, and no sample carryover for the graphitization process

Capabilities

Ultra-sensitive AMS

Mass Balance by AMS

Metabolite Profiling Using AMS

AMS for Carbon-14 Non-clinical Studies

Carbon-14 Radiolabels and AMS for Biologics

Connect with a Scientific Expert

Scientist in PPE using tweezers to load a sample into a numbered carousel while holding a 96-well plate

Advantages of AMS

An ultra sensitive technique routinely used in human AME and IVPK clinical sample analysis
Can support microtracer and full dose (microtracer) clinical study designs, and can be combined with LSC for hybrid sample analysis
The sensitivity of AMS enables the detection and quantification of low-level metabolites for drugs with complex metabolism profiles
AMS data are routinely accepted by regulatory authorities for human ADME and absolute bioavailability studies.

Ionplus accelerator mass spectrometry (AMS) system with a glowing viewport, pressure gauge, and stainless steel vacuum chamber

Standard Clinical Designs

Mass balance and total ¹⁴C-quantification (total radioactivity) by AMS
LC+AMS with online high-resolution mass spectrometry quantitation and identification of ultra-low level metabolites
Absolute bioavailability IVPK / IVMT Studies: Concomitant therapeutic extravascular/¹⁴C IV dosing for absolute bioavailability
¹⁴C dose solution analysis for low specific activity ¹⁴C dose preparations

Capabilities

Clinical & Non-clinical Support: ADME, absolute bioavailability, PK, metabolite safety (MIST)
Sample Types: Plasma, blood, urine, faeces, bile, CSF, expired air, tissues, PBMCs
Instrumentation
Ionplus50kV LEA – low energy, gaseous (¹⁴CO₂) AMS for rapid sample analysis
NEC 250kV SS-AMS – ultra-sensitive, graphite (¹⁴C) with dual ion sources, for high volume sample analysis (>2,000 samples/week)
Software: 21 CFR Part 11 compliant, audit trail, automated workflows (Ionplus LEA only)

Pharmaron Hoddesdon AMS team of seven scientists in PPE beside the Ionplus accelerator mass spectrometry system

Benefits of AMS with Pharmaron

Global Capabilities Dedicated labs in the US, UK and China providing global access to world-class AMS expertise
Accelerated Timelines: End-to-end integrated ¹⁴C metabolism programs including radiosynthesis, non-clinical and clinical support
Cost Efficiency: Minimal GMP and human dosimetry requirements
Regulatory Acceptance: regulatory compliant for FDA/EMA/MHRA/JMHW/TSA submissions
High Quality Data: Rich, quantitative datasets for confident decision-making and de-risking