Ion mobility Mass Spectrometry to enhance specificity of Metabolomic profiling with Mass Spectrometry Imaging

Mass Spectrometry imaging offers the chance to identify molecules in tissue sections and create regional maps of their locations. In our lab we focus on small molecular species in the metabolome, many of which are present in isomeric forms e.g. leucine and isoleucine. Our particular interest lies with steroids, present as stereo-isomers, some of which are active and others inactive (e.g. testosterone and DHEA).

Combination of 2 molecule images and a drift time vs relative intensity graph
Stereoselective detection of isomers of testosterone following derivatisation following ion mobility separation.

Quantitation of specific subsets can be readily achieved using chromatographic means to separate isomers, however this approach is not suitable when sampling directly from tissue surfaces and we are exploring ion mobility separation, recently installed in our lab, as an orthogonal approach to separate isomeric species. Specifically, we are developing stereospecific derivatisation approaches, designed computationally, to enhance the difference in collision cross-section and allow individual isomers to be mapped specifically. This approach is also being applied to lipidomic analysis on tissues.

References

  1. Cobice DF, Livingstone DEW, Mackay CL, Goodwin R, Smith L, Walker BR, Andrew R (2016) Spatial distribution of androgens in rodent testis by Mass Spectrometry Imaging.  Anal Chem, 88:10362-10367; PMID:27676129; PMC5102453.
  1. Faqehi AMM, Cobice DF, Naredo G, Gibb FW, Upreti R, Beckett GG, Walker BR, Homer NZM, Andrew R (2016) Derivatization of estrogens enhances specificity and sensitivity of analysis of human plasma and serum by liquid chromatography tandem mass spectrometry, Talanta, 151:148-56. PMID 26946022, PMC4791381.

Researchers 

Shazia Khan, Natalie Homer, Abdullah Faqehi, Ioannis Stasinopoulos 

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