Thermo Fisher Scientific Inc., the world leader in serving science, introduced Thermo Scientific MetQuest, its software solution that enables laboratories to take full advantage of powerful Thermo Scientific Orbitrap mass spectrometry (MS) high-resolution accurate-mass (HRAM) full-scan data to perform quantitative metabolic stability studies and identify putative metabolites in a single injection. MetQuest software is designed to provide researchers performing drug metabolism and pharmacokinetic (DMPK) studies a significant time and cost savings when compared to traditional multiple reaction monitoring (MRM) methods. MetQuest software will be demonstrated at the Salt Palace Convention Center Salons 250BCEF, May 24 – May 26, 2010 during the ASMS Conference on Mass Spectrometry and Allied Topics in Salt Lake City, Utah.
In combination with the industry-proven Thermo Scientific LTQ Orbitrap or Exactive families of liquid chromatography/mass spectrometry (LC/MS) systems, MetQuest software enables researchers to routinely perform quantitative and qualitative analyses in the same run. This solution is designed to offer substantial time and cost savings compared to triple quadrupole MRM approaches for metabolic studies. Publications from Zhang et al and Bateman et al report that quantitative results, including precision, accuracy, linearity and sensitivity for parent drugs and their metabolites, are comparable to those for established triple quadrupole MRM methods.
“Obtaining both quantitative and qualitative information more effectively and earlier in the discovery process is paramount for the pharmaceutical industry,” said Patrick Bennett, director of marketing for scientific instruments at Thermo Fisher Scientific. “MetQuest software allows users to quantify and identify compounds and their metabolites simultaneously, and interrogate data later for additional information without having to re-run the entire experiment, which typically includes sample preparation and LC/MS analysis. This turn-key solution offers significant benefits to the industry and will revolutionize the way LC/MS experiments are performed in DMPK labs.”
Understanding and documenting the metabolism of drug candidates is a key step in early-stage drug discovery. Traditionally, triple quadrupole systems using MRM methods have been used for compound quantitation. While the specificity of MRM is a key strength of these systems, it is also a limitation. MRM methods are effective in detecting a particular compound, but information about other components present in the sample, e.g. metabolites, may not be captured unless an MRM method is pre-defined to detect them. It also requires time-consuming selection and optimization of MRM parameters, such as precursor ions, product ions, declustering and collision energies, for each target analyte of interest. The time, effort and skill level required is significant for laboratories that must analyze many new chemical entities every day.
The patented Orbitrap technology is ideal for compound identification and high-throughput screening for simultaneous qualitative and quantitative analyses. Its ultra-high mass resolution up to 100,000 filters out chemical noise such as isobaric interferences from biological matrices, enabling low detection limits and fewer false positives. The patents-pending processing methods in MetQuest software have been specifically developed to automatically process full-scan high resolution data for compound identification from even the most complex biological matrices without the need for pre-defined mass-to-charge values. Because MetQuest software does not require time-consuming MS/MS method development and optimization, acquisition methods are more simple to set up and a single method can be used for multiple compounds. The automated generation of metabolic stability plots from the processed data saves time compared to manual generation of plots using other software.
Date: May 24, 2010
Source: Thermo Fisher Scientific Inc.
Filed Under: Drug Discovery