In-vitro metabolite profiling of by LC-MS/MS Tejaswini Kailas Jadhav MS (Pharmaceutical Analysis) NIPER-A

KEYWORDS

METABOLITE PROFILING Metabolites are the intermediates and products of metabolism. The measurement and interpretation of the endogenous metabolite profile from a biological sample (typically urine, serum, or biological tissue extract) have provided many opportunities to investigate drug and metabolite that are present in body.

DMPK studies is most important part during process of drug discovery, in-vitro ADMET screens, thereby accelerating the drug discovery process. DRUG DISCOVERY

Approaches in Metabolite profiling Metabolic stability Reaction phenotyping Metabolite identification Rate and nature of metabolism in in-vitro species Reactive metabolite formation Enzyme induction and enzyme inhibition-DDI

IN-SILICO PREDICTION Meta Print 2D METASITE SYBYL METEOR Metabol Expert

PROTEIN PRECIPITATION LIQUID-LIQUID EXTRACTION SOLID PHASE EXTRACTION EXTRACTION

MASS HPLC LC- NMR GC-MS LC- MS/MS LC-ICP- MS FT-IR RAMAN TOF Q-TOF ION TRAP QqQ ORBITRAP ANALYTICAL TECHNIQUES

LC-MS/MS Mass spectrometry plays a key role in drug metabolite identification, It has improved accuracy and stability, along with new data processing techniques, has improved the quality and productivity of metabolite identification processes. LC-MS/MS

Incubation of test drug sample with hepatocytes/HLM will lead to formation of Phase 1 (Oxidation / Reduction / hydrolysis) and Phase 2 conjugated metabolites. Which will be identified by validated LC-MS/MS method. Metabolism (percentage of test compound metabolized after a certain time) and qualitative determination of metabolite pattern (minor, intermediate, and major abundance of each metabolite) EXPECTED OUTCOMES

TEJASWINI KAILAS JADHAV MS(PHARMACEUTICAL ANALYSIS) NIPER-A