Science Pool

Echo MS in High Throughput ADME

Posted by Evotec on Jan 18, 2023 6:55:44 PM

The Echo® MS system, developed by Sciex, uses Acoustic Ejection Mass Spectrometry (AEMS). This chromatography-free technology generates sample droplets and introduces small reproducible volumes of 2.5nL (scalable to 25nL with multiple injections) to the mass spectrometer via an Open Port Interface with minimal carryover. It not only reduces sample requirements, it also facilitates dramatic increases in throughput with the potential to run 1 second cycle times. Despite these advantages, current potential limitations include reduced sensitivity compared to conventional LC-MS/MS and interference due to lack of separation.

In this poster, we focus on:

  • the evaluation of the Echo® MS technology for its application in routine ADME screening
  • a comparison of the Echo® MS with established, routine LC-MS/MS methods for the analysis of samples generated from microsomal stability and cytochrome P450 (CYP) inhibition assays

Read our poster to learn more about our research!

LEARN MORE

 

 

 

Tags: Posters, ADME/DMPK

Addressing the Challenges of Non-Specific Binding in a HT-ADME Environment

Posted by Evotec on Nov 1, 2022 11:59:59 AM

During analysis of samples from HT-ADME screening, non-specific binding can cause challenges due to accumulation within the analytical system. This can result in poor peak shape, low sensitivity, increasing back pressure/pressure spikes, carryover or system clogging.  

In this poster, we focus on:

  • the evaluation of the WatersTM Acquity Premier UPLC in conjunction with the Acquity Premier HSS T3 column technology which contain an inert coating specifically formulated to eliminate analyte/surface interactions
  • a comparison with standard UPLC technology
  • details on the benefits of using the Waters AcquityTM system in terms of chromatographic performance and sensitivity

Read our poster to learn more about our research!

LEARN MORE

 

 

 

Tags: Posters, ADME/DMPK

Screening for Drug-Induced Effects on Cholesterol Metabolism

Posted by Evotec on Nov 1, 2022 10:20:02 AM

The cytochrome P450 enzyme, CYP46A1, is predominantly expressed in the brain and plays a major role in cholesterol metabolism by converting cholesterol to 24-hydroxy cholesterol.

In this poster, we focus on:

  • the development and validation of an in vitro high throughput screening platform for characterisation of inhibitors and activators of CYP46A1
  • a comparison of testosterone with cholesterol as a potential replacement probe substrate for studying CYP46A1 metabolism
  • data generated from a screening cascade of 2321 FDA approved drugs

Read our poster to learn more about our research!

LEARN MORE

 

 

 

Tags: Posters, ADME/DMPK

Everything You Need to Know about ADME

Posted by Evotec on Oct 25, 2022 10:48:55 AM

Our popular, easy-to-follow guide: 'Everything you need to know about ADME' is now on its 5th edition.

Read about:

  • an in-depth overview of physicochemical properties, drug metabolism, permeability and drug transporters, drug-drug interactions and plasma protein binding
  • an assessment for current methods available for determining ADME properties 
  • how ADME data are interpreted and used
  • relevance to the regulatory guidance

LEARN MORE

Tags: Guides, ADME/DMPK

Using RIS to Improve Risk Assessment of CYP Induction

Posted by Evotec on Jul 12, 2022 12:25:10 PM

Watch the webinar to learn more about recent updates in CYP induction!

 


About the Webinar

Cytochrome (CYP) P450 induction is a well-established mechanism for increased prevalence of DDIs. Whilst its study in vitro has been described in regulatory guidance for over 20 years, data interpretation methods and details for study design have evolved and the best approaches for study of small molecules and other therapeutics are still being discussed within CROs, pharma and biotechs.

In this webinar our expert, Katie Plant, describes the most recent updates in CYP induction. By reviewing and consolidating literature and recent perspectives from Innovation and Quality Induction Working Group (IQ IWG) alongside the regulatory guidance, this provides a comprehensive overview and outlines the recommended approach to assess CYP induction in vitro. When supported by well-designed in vitro assays and batch qualification using a known set of CYP3A4 inducers, relative induction score (RIS) correlation analysis serves as a useful tool enabling the magnitude of clinical CYP3A4 induction to be predicted and used to support decision-making for investigating potential DDI risk.


About the Speaker

 

Plant,KatieRSZ

Katie Plant

Principal Scientist | Cyprotex Discovery Ltd

Katie Plant is a Principal Scientist in the Drug Metabolism group at Cyprotex, UK, responsible for operational delivery of high-throughput screening assays covering metabolic stability, enzyme inhibition and induction, alongside supporting clients in designing and interpreting DDI studies to support regulatory submission, supporting R&D and bespoke studies and driving continuous improvement projects.

Watch the webinar to learn more!

[hs-form id="f0365c7a-f5d3-411a-a11b-097b618db7a5" show="hide on login" url="https://news.evotecsciencepool.com/hubfs/Sciencepool/Videos%20and%20Webinars/Cyprotex%20webinars%20and%20videos/cyp-induction-webcast-on-demand-july2022.mp4"]

Tags: Videos & Webinars, ADME/DMPK

Use of Quantitative LC-MS/MS Methods to Compare Conventional Blood Collection and Microsampling in Non-human Primate

Posted by Evotec on Jun 21, 2022 2:52:09 PM

Toxicokinetic evaluation is a regulatory and scientific requirement in the drug development process. To obtain plasma, blood is generally withdrawn by a conventional venous collection method. Microsampling is a less invasive sampling technique, which allows to reduce the stress correlated to the conventional blood sampling and to decrease the number of rodents for a preclinical study. The implementation of microsampling in particular, in non-human primate can reduce the stress and promote a positive interaction with technical staff which improves the overall well-being of the animal (refinement).


In this poster we summarise the work done to evaluate the possible influence of the blood sampling method on drug plasma concentrations, using LC-MS/MS methods in non-human primate for four drugs selected based on acid-base and volume of distribution properties.


The poster was presented by our expert Rossella Cardin at the 24th International Reid Bioanalytical Forum held in Cambridge, UK, on June 13-16, 2022.

 

DOWNLOAD

Tags: Posters, ADME/DMPK, IND Enabling Studies/Preclinical Development, Toxicology & Safety

INDiGO Fact Sheet

Posted by Evotec on Apr 20, 2022 1:56:21 PM

INDiGO is the fastest and most efficient platform to bring a program from candidate selection through IND and beyond.

Once your clinical candidate is selected, this fully-integrated clinical-enabling package provides inter-disciplinary coordination of all aspects of drug development, conducted and managed by a dedicated Evotec team, and usually at a single Evotec site.

Key features:
  •  Accelerating your drug discovery and research programs through interdisciplinary integration and expert coordination of all activities “under one roof”
  • Industry-leading timelines, taking your program from the selection of an optimal clinical candidate to regulatory submission typically in less than 52 weeks
  • Expert management by experienced, dedicated project managers and drug development professionals
  • Seamless knowledge transfer across disciplines, maximizing the quality and efficiency of the overall development package
  • Custom-designed, flexible development plans that allow for real-time adjustments and adaptability to unforeseeable scientific outcomes
  • Excellence in project governance, performance review and issue escalation management
DOWNLOAD

 

Tags: Fact Sheets, Formulation & CMC, ADME/DMPK, IND Enabling Studies/Preclinical Development, Toxicology & Safety

Cytochrome P450 Induction Fact Sheet

Posted by Evotec on Apr 7, 2022 2:50:14 PM

Download this fact sheet to learn more about cytochrome P450 (CYP) induction including:

  • Background information
  • Assay details and protocol summary
  • Data generated in the CYP induction assay
DOWNLOAD 

 

Tags: Fact Sheets, ADME/DMPK

Cytochrome P450 Induction: Relative Induction Score (RIS) Fact Sheet

Posted by Evotec on Apr 7, 2022 2:47:22 PM

Download this fact sheet to learn more about cytochrome P450 (CYP) relative induction score (RIS) including:

  • Background information for the CYP induction RIS method
  • Assay details and protocol summary for the CYP induction RIS method
  • Data generated in the CYP induction RIS assay
DOWNLOAD 

 

Tags: Fact Sheets, ADME/DMPK

Hepatocyte Stability Fact Sheet

Posted by Evotec on Apr 7, 2022 1:20:01 PM

Download this fact sheet to learn more about hepatocyte stability including:

  • Background information
  • Assay details and protocol summary
  • Data generated in the hepatocyte stability assay
DOWNLOAD 

 

Tags: Fact Sheets, ADME/DMPK