Science Pool

Download this fact sheet to learn more about the microsomal stability assay including:

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

Download this fact sheet to learn more about the MDCK-MDR1 permeability assay including:

• Background information
• Assay details and protocol summary
• Data generated in the MDCK-MDR1 permeability assay

Learn more about the low clearance Hurel co-culture assay including:

• Background information
• Assay details and protocol summary
• Data generated in the low clearance Hurel co-culture assay

Learn more about the human SLC transporter substrate identification assay including:

• Background information
• Assay details and protocol summary
• Data generated in the SLC transporter substrate identification assay

Learn more about the P-gp substrate identification assay including:

• Background information
• Assay details and protocol summary
• Data generated in the P-gp substrate identification assay

Drug-drug interaction (DDI) studies are an important part of the regulatory drug development process. The US FDA, EMA and Japanese PMDA have issued guidance on the conduct of these DDI studies, however, a harmonised guidance is currently under review (ICH M12) and is expected to be adopted in April 2024. The risk of DDI can be assessed in vitro and data analysed using models of varying complexity.  As identifying potential safety issues is the main purpose of these studies, many of the models have been developed to over-estimate the risk of DDI .This, however, needs to be balanced with the risk of false positives and the potential of unnecessary clinical DDI studies which are expensive and time consuming to perform. It is essential, therefore, to choose the most accurate model when analysing data from in vitro DDI studies.   

In this poster, we focus on:

• an evaluation of the various models for predicting clinical CYP3A4 induction risk from in vitro data
• a comparison of basic R₃ values (with and without a scaling factor) with correlation methods (relative induction score (RIS) and I_max/EC₅₀ values)

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LC-MS/MS produces highly sensitive, specific and reproducible data, however, throughput can be a limitation and this can lead to a bottleneck in sample analysis from pharmacokinetic (PK) studies.

In this poster, we focus on:

• the development of ultra-fast separation chromatography to improve efficiency of sample analysis in small molecule PK studies
• a comparison of the rapid separation method with conventional column technology for the analysis of plasma and blood samples from a PK study

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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

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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 Waters^TM 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 Acquity^TM system in terms of chromatographic performance and sensitivity

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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

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