IMSERC - Clinical Pharmacology Core

CPC strongly suggests that consultation occurs at the proposal stage to ensure sufficient sampling is defined to answer the scientific question posed. Consultation with Prof. Michael Avram is free of charge.

CPC will perform GLP-like validation of assays to ensure robustness, precision, and accuracy. Typical acceptance criteria are > 80% recovery (extracted vs. neat), <15% variability within run, and <20% variability run to run over 3 independent sample preparations in a 48 hour period.

All plasma samples will be run in duplicate. Typically 250 uL plasma is required and CPC recommends that an independent sample be stored at an alternate location until results are published.

CPC will provide data from assay validation, assay procedure for publication and concentration data for each sample.  Additional modeling and generation of manuscripts can be performed on a fee-for-service basis.

For long-term studies, samples can be stored at -80C in freezers located within IMSERC prior to analysis. Samples for paid studies will be kept for up to 5 years or until publication. If interim measurements are requested, the assay must be revalidated for each analysis. For jobs > 70 samples, the revalidation cost is waived. For jobs less than 70 samples, the cost to revalidate the assay will be passed on to the project.

CPC supports non-GLP studies needed for IND and includes development of assays that can be transferred to GLP labs and generation of pharmacokinetic data from animal models needed to begin clinical trials. Contact Prof. Michael Avram to discuss design of studies and for assistance in grant writing to fund robust studies. Validation and success criteria are the same as investigator initiated studies. Modeling of results can be performed on a fee-for-service basis by Prof. Avram if needed.

In order to test bioavailability of novel compounds, CPC provides rapid analysis of plasma samples from animal models. CPC collaborates with the Developmental Therapeutics Core to obtain IACUC approval for studies and generate samples.

CPC staff will spend approximately one day developing an assay. Target concentration range is 1 ng/mL - 1 ug/mL in plasma. Success criteria for analysis is LLOQ > 50 ng/mL  and greater than 50% recovery. If additional sensitivity is required, development will occur on a best effort basis and charged at a daily rate. Up to 30  samples can be run in duplicate as part of the analysis. Depending on the sampling plan and data quality, data can be modeled for a 2 hour consultation charge.

In order to test bioavailability of novel compounds, CPC provides rapid analysis of tissue samples from animal models, including brain and liver. CPC collaborates with the Developmental Therapeutics Core to obtain IACUC approval for studies and generate samples.

CPC staff will spend approximately one day developing an assay. Target concentration range is 1 ng/g - 1 ug/g in plasma. Success criteria for analysis is LLOQ > 50 ng/g  and greater than 50% recovery. If additional sensitivity is required, development will occur on a best effort basis and charged at a daily rate. Up to 30  samples can be run in duplicate as part of the analysis. If multiple tissue types are requested at the same time, CPC staff will attempt to develop methods in parallel. If complete analysis takes less than 2 days/tissue type, the savings will be passed on to the project.

CPC performs analysis of cell lysates and microsomal studies requiring minimal sample preparation on a best effort basis. Typical human and rodent microsomal studies take one day and are billed at one day instrument time and 5 hours staff time.

Faculty designing experiments in a proposal are encouraged to collaborate with Prof. Avram to ensure studies are appropriately designed and resourced. In cases where data modeling or manuscript preparation assistance is needed and Prof. Avram does not have effort on the project, assistance can be provided on a fee-for-service basis.

Groups requiring repetitive analysis of similar samples may perform analysis by reserving the SCIEX 6500 on a daily basis. CPC staff must perform all method development and approve experiments. Method development is performed on a fee-for-service basis. This service is only recommended for groups expecting to utilize the instrument at least once per month.