search.noResults

search.searching

dataCollection.invalidEmail
note.createNoteMessage

search.noResults

search.searching

orderForm.title

orderForm.productCode
orderForm.description
orderForm.quantity
orderForm.itemPrice
orderForm.price
orderForm.totalPrice
orderForm.deliveryDetails.billingAddress
orderForm.deliveryDetails.deliveryAddress
orderForm.noItems
Perspective Metz, Baker, Schymanski et al.


Figure 4. Workflow for the identification of small molecules based on experimental and theoretical collision cross sections and accurate mass. Untargeted SPE-ion mobility spectrometry-MS measurements (green box) provide experimental collision cross section (CCS) and accurate mass m/z values for sample molecules, as well as their isotopic signatures. Independently, theoretical CCS calculations (blue box) augment the contents of a CCS and accurate mass reference library. Separately, molecules that cannot be identified by matching to the CCS and accurate mass reference library or to MS/MS libraries are analyzed based on their masses to generate candidate molecular formulas, which are then converted into 3D structures for CCS prediction (purple box).


then measured for the same molecules and using


identical instrumentation in three independent labo- ratories with RSD < 5% for 99% of molecules stud- ied [117]. The authors also used computational meth- ods to predict CCSs for the same 125 metabolites and found good agreement with the experimentally deter- mined CCSs, with R2


of 0.93. Stephen et al. coupled


DTIMS with 1D and 2D LC-MS in untargeted anal- ysis of wastewater samples and used an in-house CCS reference database containing 500 entries together with accurate mass to identify 22 and 53 different c ompounds, r espectively [92].


Conclusion In summary, comprehensive characterization of expo- sure is challenging due to the thousands of structur- ally and physicochemically diverse chemicals one encounters per day, and which may be present at any given time in some amount in body compart-


37 Bioanalysis (2017) Bioanalysis (2017) 9(1), 81–98(1)


ments. Complicating this, when employing metabo- lomics approaches, is the presence of the endogenous metabolome and its localized or systemic response to exposure. Thus, the potential chemical space that can be measured is vast, and untargeted data acqui- sition approaches are best suited to comprehensively m easure the exposome. Advancing measurement technologies, including


those based on or incorporating DTIMS, are enabling increasingly higher coverage of sample molecular compositions. The volume of data corresponding to these new chemical observations will require new informatics methodologies to confidently assign as many identifications as possible. To address this challenge, we propose that accurate, computationally predicted CCS values can facilitate the broad identi- fication of detected molecules in combination with accurate mass and MS/MS spectra, when a vailable, and possibly with just accurate mass


future science group


Page 1  |  Page 2  |  Page 3  |  Page 4  |  Page 5  |  Page 6  |  Page 7  |  Page 8  |  Page 9  |  Page 10  |  Page 11  |  Page 12  |  Page 13  |  Page 14  |  Page 15  |  Page 16  |  Page 17  |  Page 18  |  Page 19  |  Page 20  |  Page 21  |  Page 22  |  Page 23  |  Page 24  |  Page 25  |  Page 26  |  Page 27  |  Page 28  |  Page 29  |  Page 30  |  Page 31  |  Page 32  |  Page 33  |  Page 34  |  Page 35  |  Page 36  |  Page 37  |  Page 38  |  Page 39  |  Page 40  |  Page 41  |  Page 42  |  Page 43  |  Page 44  |  Page 45  |  Page 46  |  Page 47  |  Page 48  |  Page 49  |  Page 50  |  Page 51  |  Page 52  |  Page 53  |  Page 54  |  Page 55  |  Page 56  |  Page 57  |  Page 58