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| Preclinical Services |
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Attomole-level (10-18 M)
Bioanalytical Services:
Preclinical Challenges and Solutions As a specialty contract laboratory, Accium BioSciences offers highly sensitive bioanalytical services that solve challenging problems in preclinical development. Our Accelerator Mass Spectrometry (AMS) services deliver 103-fold improvement in sensitivity compared to most LC/MS/MS methods while reducing the specific activity required for the test product by 106-fold.
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 Labeling 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.
Pharmacokinetic (PK) study of a compound investigated in a rat and mouse model. Rats were administered non-labeled compound, 4mg/kg by i.v. with HPLC detection. Mice were administered 14C-labeled compound, 4 mg/kg by i.v. with AMS detection. The mouse study required synthesis of less test material, had similar PK with rat model and showed longer plasma retention.
Detailed biodistribution study of a 14C-labeled compound in mice. Distribution of the compound into a wide range of tissues was measured by AMS. Samples were homogenized in buffer and total 14C detected with attomole (10-18M) sensitivity. Metabolites can be profiled by first fractionating the samples by HPLC followed by AMS measurement of each fraction.
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Please call +1 (206) 281-3915 to learn more information about our AMS bioanalytical services. |
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