Simultaneous assessment of drug metabolic stability and identification of metabolites using HPLC-Chip/ion trap mass spectrometry can effectively identify metabolites, save time and improve work efficiency
This document describes a method for simultaneously measuring drug metabolic stability and identifying metabolites using automated nanospray LC/MS. The study utilizes the Agilent 6330 Ion Trap LC/MS coupled with an HPLC-Chip to analyze the drug buspirone at a concentration of 1 pM following incubation with rat liver S9 fractions. This approach allows for both assays to be performed in a single run, offering high sensitivity and efficiency compared to traditional methods that require separate incubations. The high sensitivity of the HPLC-Chip/MS approach enabled the detection of metabolites at very low substrate concentrations, which is critical for early-stage drug discovery.
| Flow rate | 0.3 pL/min |
|---|---|
| Injection volume | 1 pL |
| Drying gas flow | 3 L/min |
| Drying gas temperature | 300 °C |
| Capillary voltage | -1800 V |
| Scan range | 100-500 m/z |
The Agilent 6330 Ion Trap LC/MS is used for the analysis.
The assessment is performed at a substrate concentration of 1 pM.
The incubation is carried out at 37 °C for 0 minutes and 28 minutes.
The flow rate was set to 0.3 pL/min.