Bioanalytical assay development and validation for trace level analysis of drugs and/or metabolites in biological fluids and tissues:
Method development using HPLC for high capacity LC for routine analysis
Capabilities in LC/MS/MS for applications in both Electrospray (ES) and atmospheric pressure chemical ionization (APCI) interfaces for quantitative analysis and qualitative drug/drug metabolite identification
Solution properties & Preformulation (activities focus on physico-chemical characterization)
Permeability: Caco-2 monolayers are utilized to evaluate structural absorption relationship in discovery to identify suitable oral drug candidate
Evaluation as substrate for P-glycoprotein
In vitro metabolism:
Primary metabolic stability:
Screening is done using liver S9 fraction, microsomes and cDNA expressed isozymes from different animal species (mouse, rat, rabbit, guinea pig, dog and monkey) and humans.
Secondary evaluation:
CYP 450 pathway identification for metabolites and greater understanding of the principal enzyme (CYP450) involved in drug metabolism.
Preliminary enzyme kinetic experiments in vitro to determine km and Vmax
Tertiary evaluation:
Inhibition of CYP 450 isozymes. Primary drug-drug interaction & its implication in drug development.
Pharmacokinetic studies in rodents with bioanalysis & PK parameter calculations
