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How is Meteor Nexus Used?

Meteor Nexus is the expert knowledge-based software for the prediction of metabolic fate in mammals. Using structure activity relationship (SAR) analysis, Lhasa’s scientific experts have developed a comprehensive dictionary of biotransformations covering both phase I and phase II metabolism.

Meteor can also be used for unusual metabolism, metabolite elucidation via mass defect analysis, and is compatible with some mass spec software. 

Unusual Metabolism

The Use of Meteor for Unusual Metabolism

Some Meteor users reserve use of an in silico prediction tool for cases where there is evidence of unusual metabolism, for example where an unusual biotransformation occurs where there is no precedence for it, or the biotransformations occur in an unusual combination or order.

In this instance, Meteor is used with the Absolute/Relative Reasoning methodology, with the aim of providing a large resulting prediction. The results can then be searched to identify the unusual biotransformation(s) and view the suggested biotransformation pathway associated with its generation.

 

 

 

 

 

 

Figure 1: The ring contraction of 2,2,6,6-Tetramethylpiperidines to 2,2-Dimethylpyrrolidines is an example of a biotransformation displaying unusual chemistry.

 

 

 

 

 

 

Figure 2: Meteor’s Dictionary contains the Biotransformation 459 which covers this type of reaction. 

Mass Defect Analysis

The Use of Meteor for Metabolite Elucidation via Mass Defect Analysis

Mass defect is defined as the difference between the exact mass of a compound and its integer value. For example quetiapine has the following molecular properties:

 

Molecular Formula: C21H25N3O2S

Exact Mass: 383.16675

Nominal Mass: 383

Mass Defect: 383.16675 - 373 = 0.16675

 

One of the known active metabolites of quetiapine is 7–hydroxyquetiapine:

 

Molecular Formula: C21H25N3O3S

Exact Mass: 399.16166

Nominal Mass: 399

Mass Defect: 399.16166 - 399 = 0.16166

 

Subtracting the mass defect values of the metabolite and the parent gives the following result:

0.16166 - 0.16675 = -0.00509

Using the “Query Mass Defect” filter in Meteor Nexus with the value -0.0051 (Tolerance = 1E-5) will only display metabolites where the molecular formula change is +O or has a mass increase of +16 e.g. hydroxylation, epoxidation or S– or N–oxidation.

Mass defect filtering is not limited to Phase I oxidative biotransformations. It can also be applied to dehydration, nitro reduction and dealkylation reactions and Phase II biotransformation such as glucuronidation (+0.0321). In summary, filtering by mass defect is a convenient way to reduce the number of metabolites that are displayed after a prediction has been made.

This video provides an overview on Mass Defect and Mass Defect Shift, and how this can be used within Meteor Nexus. 

 

Mass Spec Software

The Use of Meteor with Mass Spec Software

Meteor Nexus can be used to help elucidate the likely chemical structures detected by a mass spectrometer and help predict likely metabolic pathways. Following processing of the parent compound through Meteor, a range of filters can be applied to provide a results tree that is consistent with the experimental findings.

Users can export a report from Meteor that includes details of the mass difference between the parent compound and the predicted metabolites. This report can then be used in conjunction with Mass Spec Software, to determine whether peaks in the Mass Spec could match with metabolites predicted by Meteor.

Meteor results can be used with a range of mass spec software, including those provided by the following vendors:

  • Agilent Technologies
  • Bruker
  • Shimadzu
  • ThermoFisher Scientific
  • Waters

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