Agilent Simultaneous determination of metabolic stability and identification of buspirone metabolites using multiple column fast LC TOF mass spectrometry 说明书用户手册.PDF
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Simultaneous determination of metabolic 
stability and identification of buspirone 
metabolites using multiple column fast 
LC/TOF mass spectrometry 
Application Note 
                                                       Edgar Naegele 
Abstract 
A recent trend in the drug discovery and development process is to 
shift the starting point of drug metabolism and pharmacokinetic 
(DMPK) studies to a time as early as possible in the development chain 
to address potential issues in parallel with the optimization of the drug’s 
lead structure. There is a strong need for assay methods to determine 
early ADME parameters such as metabolic stability and metabolite 
identification. It is necessary to work with a fast LC/MS system which 
provides the necessary functionalities together with high speed and res- 
olution to handle the resulting large number of samples. 
In this Application Note a metabolic stability profile of buspirone 
will be acquired by the Agilent 1200 Series Rapid Resolution LC/TOF 
system on a short Rapid Resolution High Throughput (RRHT) column. 
Simultaneously, the main metabolites will be identified in the same 
experiment by the automated use of a long RRHT column, which 
provides the necessary high resolution. 
Introduction                                 tem must be able to use multiple              umn. Simultaneously, the main 
                                             columns in a thermostatted col-               metabolites will be identified in 
In modern pharmaceutical drug 
                                             umn oven for various analytical               the same experiment by the auto- 
development it is of crucial impor- 
                                             methods and high throughput                   mated use of a long RR column, 
tance to know the adsorption, dis- 
                                             functionalities such as overlapped            which provides the necessary high 
tribution, metabolism and
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