This document introduces the application of Agilent RapidFire/MS systems for high-throughput in vitro ADME analysis. The authors emphasize the importance of analyzing cytochrome P450 (CYP) inhibition and the need to evaluate a larger number of samples. They propose a fast, efficient, and cost-effective method for analysis.
Agilent Technologies presents an application note on high-throughput in vitro ADME analysis using their RapidFire/MS systems. The document focuses specifically on Cytochrome P450 (CYP) inhibition assays, a critical step in drug discovery to prevent adverse drug-drug interactions.
The text details how Agilent RapidFire/MS systems combine sample processing with triple quadrupole or time-of-flight mass spectrometry. It validates the system against traditional LC/MS/MS methods using FDA-recommended drug probes for various CYP enzymes, demonstrating equivalent results with significantly faster run times.
| Run time per sample (RapidFire) | approximately 6 s |
|---|---|
| Run time per sample (LC/MS/MS) | 2-4 min |
| Throughput increase | greater than 10-fold |
The FDA preferred substrates for CYP3A4 are midazolam and testosterone.
Yes, correlation of IC50 values indicates that the RapidFire system produces equivalent results to traditional LC/MS/MS.