Science Pool

Our popular, easy-to-follow guide: 'DDI Regulatory Guidance' is now on its 3rd edition.

Read about:

• an easy to follow summary and comparison of the latest DDI guidance from the FDA and the EMA
• a focus on reaction phenotyping, cytochrome P450 inhibition, cytochrome P450 induction, drug transporter substrate studies and drug transporter inhibition
• an overview of the regulatory methods and interpretation of data

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The skin is the largest organ in the human body. It contains enzymes capable of drug metabolism.

In this presentation, we focus on:

• the physiology of the skin and an overview of skin enzymology
• the role of skin metabolism in absorption, efficacy, homeostasis, drug delivery and toxicity
• adverse reactions in the skin including the mechanism behind skin sensitisation
• in vitro methods for investigating skin metabolism

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LC-MS provides the analytical endpoint for most discovery ADME assays. There is a constant drive to reduce LC-MS run times whilst maintaining quality. 

In this presentation, we focus on:

• a comparison of triple quadrupole MS/MS vs TripleTOF MS
• validation data for performance of the TripleTOF MS 
• use of the TripleTOF in high throughput ADME screening including intrinsic clearance assays and soft spot analysis.

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Due to an aging population, polypharmacy is increasing. Drug-drug interactions account for 5% of UK hospital admissions, and are a particular concern for common co-meds such as statins.

In this presentation, we focus on:

• a background to drug-drug interactions (DDI)
• the use of the mechanistic static models in the prediction of transporter-mediated DDI
• a comparison of the different published models and their performance 

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Reducing the sample cycle time for LC-MS analysis is critical in increasing throughput and improving efficiency.

In this poster, we focus on:

• the development of a ultra-fast chromatography method with rapid cycle time
• the analysis of the sensitivity, linearity, reproducibility, robustness and matrix effects for the method
• applicability to intrinsic clearance determination

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In order to accurately predict human pharmacokinetics and efficacious dose, a robust measurements of clearance is essential.

In this poster, we focus on:

• a novel primary human hepatocyte media supplement (HepExtend^TM)
• a comparison of HepExtend^TM with the widely used CM4000 with and without a Geltrex overlay
• a correlation of scaled in vitro human intrinsic clearance with in vivo human intrinsic clearance

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Real time mass defect filtering (MDF) on independent acquisition (IDA) scans enable the generation of simultaneous selective MS and MSMS data in one injection.

In this poster, we focus on:

• the use of high resolution mass spectrometry and mass defect filtering combined with rapid chromatographic run times and semi-automated commercial software for soft-spot identification of metabolites
• demonstration of the metabolite soft-spot method using verapamil and dextromethorphan

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Pre-incubating with inhibitor can influence inhibitory potency for some drug transporters such as OATP1B1. It is thought that this phenomenon is a consequence of the time taken for some inhibitors to accumulate inside the cell.

In this poster, we focus on:

• a comparison of a 30 min pre-incubation time with a 15 min pre-incubation time for OATP1B1
• the impact of inhibitor pre-incubation on P-gp and BCRP inhibition in a polarised cell monolayer

Read our poster to learn more about our research!

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