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CPSA Digest 2001

New Technologies and Approaches for Increasing Drug Candidate Survivability:
Lead Identification to Lead Optimization

October 9-11, 2001

CPSA Digest 2001

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Proceedings -Tuesday, October 9, 2001

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Structure Profiling:
Application of MALDI Q-TOF Quadrupole-Time of Flight Mass Spectrometry to the Analysis of Drug Metabolites; Experiences with the QSTAR PULSARTM at Boehringer-Ingelheim

John P. Barry, Roger Dinallo, and David Joseph
Boehringer Ingelheim

Premise:
An innovation in hybrid MS technology leverages the power of quadrupole and time-of-flight instrumentation. MALDI QqTOF can operate in two modes. By using the technique initially in MS mode, researchers are able to obtain a TOF spectrum. Then, by operating in MS/MS mode, the instrument is able to select for further analysis only selected mass ranges.

The API QSTAR(TM) Pulsar Hybrid LC/MS/MS System (Applied Biosystems; ABI) and the MALDI Qq-TOF (MDS Sciex) provide high sensitivity for precursor and product ion scanning in MS/MS experiments. With rugged ion sources, reliable hardware, and the LINAC(TM) Pulsar high-pressure collision cell that pulses ions into the mass analyzer, superior mass accuracy and sensitivity can be achieved.

Value of the Technology
The use of Q-TOF technology at Boehringer-Ingelheim for metabolite structure identification has been demonstrated to offer: Sum High mass resolution Sum High sensitivity in TOF-MS and TOF/MS/MS modes Sum High mass accuracy (10 ppm or less)

Although QTOF is very sensitive, it is less sensitive than triple quadrupole MS. Pulsing using the QSTAR PULSAR gives 5-10 times more sensitivity in TOF-MS and TOF-MS/MS modes. The precision ion-scanning mode is very useful.

Links
Applied Biosystems product information

MDS Sciex product information



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