Clinical Pharmacology Analytical Core

ABSTRACT, Clinical Pharmacology Analytical Core (CPAC) The Indiana University Simon Comprehensive Cancer Center (IUSCCC) Clinical Pharmacology Analytical Core (CPAC) provides multifaceted expertise in bioanalytical methodology and clinical pharmacology to provide investigators with robust information including in vivo pharmacokinetics, drug-drug interactions, in vitro drug metabolic stability, stereoselective metabolism, metabolite identification, formulation optimization, protein binding, drug purity verification, and drug stability. CPAC's expertise in bioanalytical analysis is coupled with state-of-the-art laboratory equipment including three UHPLC triple quadrupole QTRAP mass spectrometers (LC- MS/MS QTRAP) for quantification of drugs and metabolites, two of which were recently purchased through a collaboration of the IU School of Medicine and IUSCCC, one HPLC photo diode array system, LC-UV technologies, and a Biomek 4000 liquid handling robot, all to facilitate the research and development of drugs and new chemical entities. CPAC and IUSCCC's leadership have defined three specific aims for this Shared Resource: Aim 1. Provide IUSCCC members with broad, high-quality small molecule bioanalytical services from various matrices in expedited timelines; Aim 2. Facilitate cancer drug discovery and development research by working closely with investigators and the Cancer Drug Discovery and Development Accelerator (CD3A) group to establish effective lead generation and lead optimization strategies; and Aim 3. Provide detailed pre-clinical and clinical data analysis, including non-compartmental and compartmental pharmacokinetic (PK) analysis and pharmacokinetic/pharmacodynamic (PK/PD) modeling. Through these aims, CPAC has supported CD3A and clinical investigators by providing cost-effective, validated assays to support in vitro and in vivo ADME and PK analyses of small molecules. Over the past three years, CPAC has supported 32 IUSCC investigators on numerous projects, with over 2200 service hours devoted to method development, formulation optimization, solubility assessment, protein binding, and metabolic stability and analyte quantification in over 4000 tissue and plasma samples. Over the next five years, it is anticipated that demand will continue to grow for these services and expertise to support the growing number of preclinical drug development programs supported by CD3A and advancement of candidate drug molecules towards clinical trials.