AMS PRECLINICAL STUDIES
Accium offers highly sensitive bioanalytical services that solve challenging problems in preclinical studies. Our AMS services deliver 1,000-fold improvement in sensitivity compared to most LC-MS/MS methods and 100,000-fold greater sensitivity than liquid scintialltion counting. This reduces the requirement for doses with high specific activity while significanty reducing sample size requirements.
Typical Study Design Parameters:
- Dose size: <5 nCi
- Plasma sample size: 1-10 uL
- Tissue sample size: 1-100 mg
- Plasma detection limits: 0.01 DPM/mL plasma
- Tissue detection limits: 0.01 DPM/g tissue
- HPLC fractions: 0.001 DPM/mL fraction
- No matrix or quenching effects
Researchers can now evaluate various dose regimens, routes of administration, pharmacokinetics (PK) and biodistribution using 14C-labeled compounds with specific activities in the nCi/mmol range. Our lead optimization services can help prioritize and accelerate compound ranking and lead candidate selection.
Case Studies
- Low Bioavailability PK-ADME screening of drug candidates with low bioavailability is a challenging task with conventional analytical methods. Our clients have used AMS-based methods to screen compounds with low bioavailability and fast turnover.
- Costly 14C Synthesis The extreme sensitivity of AMS detection simplifies challenging 14C-labeling projects. A lightly-labeled compound (nCi/mmol range) is all that is required for AMS-based studies. Our clients typically produce this lightly-labeled compound in-house at pilot-scale levels, which can save tens of thousands of dollars in outsourced synthesis costs.
- Limited Sample Volumes AMS quantifies 14C-compound in as little as 20 uL of plasma, urine and tissue homogenates, making possible detailed biodistribution studies in small animals. AMS protocols allow collection of multiple blood samples from the same animal over the course of a PK study, reducing the number of animals and the amount of test product required for a preclinical study. In addition, it is now possible to quantitate 14C-compound distribution into extremely small target organs or fluids.
- Highly Potent Compounds Conventional bioanalytical platforms do not have the sensitivity required for detection of highly potent drug candidates and engineered compounds. Some of these compounds are pharmacologically active at very low doses (ng/kg). The sensitivity offered by AMS allows our clients to acquire long term PK and ADME information in animals administered therapeutically relevant doses.
