ADME & DMPK Assays & Analysis
Syngene is conducting DMPK studies both in vitro ADME and in vivo PK studies and we offer these studies either as stand-alone projects (fee for service model) or as a part of collaborative Integrated Drug Discovery (IDD) program. Our state-of-the-art infrastructure which includes automation is also equipped with UPLCs and Tof platforms to churn out bio analytical data rapidly to support the fast-track drug discovery projects. Our bio-analytical scientific team is also experienced in developing customized assays and are adept in implementing protocols provided by customers on need basis.
In vitro ADME capabilities includes buffer solubility (kinetic & thermodynamic), stability in buffer, plasma, serum & simulated gastric/intestinal fluid, LogD, multi-species plasma, brain/tissue homogenate protein binding, metabolic stability and metabolite profiling with S9, microsome & hepatocytes, metabolite ID, UGT phenotyping, PAMPA, Caco-2 efflux, MDCK permeability, CYP450 inhibition & TDI , CYP phenotyping, CYP450 3A4 induction in PXR-luciferase reporter gene assay, and RBC-Plasma (Cb/Cp) partitioning in multiple species.
In vivo PK studies are offered in standard cannulated rats and mice which is a unique serial bleed PK is offered. Special studies such as bile duct cannulation (BDC) is offered for ADME investigations.In the safety assessment, in vitro safety assays are offered for evaluating liability for cardiac safety, drug-induced liver injury (DiLi), mitotoxicity, drug-drug interaction liability, and genotoxicity. We routinely run high-throughput screens for HERG binding, BSEP transporter assays and human PXR assays using radioactive and non-radioactive approaches. In addition we offer the high-content imaging based assays for cardiotoxicity evaluation in human iPSC derived cardiomyocytes, phospholipidosis assay in human hepatocytes and flow cytometry based mitochondrial toxicity assays on need basis.
- Physico-chemical properties - aqueous solubility, pH stability, Lipophilicity (Log D) and Log P
- Absorption – PAMPA, CaCo-2 and MDCK, Efflux (CaCo-2)
- Metabolism & stability - Liver microsomes (%PCR and Clint), plasma and serum stability, CYP450 inhibition includes inhibition screening (Fluorescence based/LC-MS/MS based) and time - dependent inhibition (TDI), CYP450 phenotyping and metabolite identification (LC-MS/MS) (in vitro & in vivo)
- Distribution - plasma protein binding, brain protein binding and blood-plasma distribution (Ce/Cp)
- Cytotoxicity - cell-based assays in human cell- lines
Early stage PK evaluation of NCE's in rodents:
- Discrete and cassette dosing
- Tissue distribution
- Brain-plasma distribution
- Entero-hepatic recirculation (EHC)
- Determination of fundamental PK parameters (Tmax, Cmax, AUC, clearance, oral bioavailability, volume of distribution, etc.)
Development of bioanalytical methods to support bioavailability and pharmacokinetics studies.
- HPLC -UV and LC-MS/MS based methods
- Development of efficient extraction procedures (protein precipitation, liquid- liquid extraction, solid-phase extraction)
- Development of analytical methods in presence of different matrices