Rapid Ion Mobility Separations of Bile Acid Isomers Using Cyclodextrin Adducts and Structures for Lossless Ion Manipulations

Abstract

Bile acids (BAs) constitute an important class of steroid metabolites often displaying changes associated with disease states and other health conditions. Current analyses for these structurally similar compounds are limited by a lack of sensitivity and long separation times with often poor isomeric resolution. To overcome these challenges and provide rapid analyses for the BA isomers, we utilized cyclodextrin adducts in conjunction with novel ion mobility (IM) separation capabilities provided by structures for lossless ion manipulations (SLIM). Cyclodextrin was found to interact with both the tauro- and glyco-conjugated BA isomers studied, forming rigid noncovalent host-guest inclusion complexes. Without the use of cyclodextrin adducts, the BA isomers were found to be nearly identical in their respective mobilities and thus unable to be baseline resolved. Each separation of the cyclodextrin—bile acid host—guest inclusion complex was performed in less than 1 s, providing a much more rapid alternative to current liquid chromatography-based separations. SLIM provided capabilities for the accumulation of larger ion populations and IM peak compression that resulted in much higher resolution separations and increased signal intensities for the BA isomers studied.

Distinguishing enantiomeric amino acids with chiral cyclodextrin adducts and structures for lossless ion manipulations

“…In this, the 9 m first TW region was used to accumulate ions in lieu of the ion funnel trap (for gains in sensitivity [31]) and separation was performed for 4.5 m on the first pass, followed by four additional passes (13.5 m each) for a 58.5 m total path [(4.5 m) + (4) × (13.5 m)]. CRIMP [31, 35] was applied only on the second pass (as previously described [45]) for increases in both S/N and signal intensity.…”

“…Longer path separations were performed by the use of an ion switch [33], which can route the ions either to the Agilent 6224 TOF-MS for detection or back to the start of TW1 serpentine path for another 13.5 m of separation (9 m TW1 + 4.5 m TW2) for SLIM SUPER analyses. Compression ratio ion mobility programming [31, 35] (CRIMP) was applied in the same manner as previously described [45]. Briefly, a stuttering (i.e.…”

Enantio‐separation of pregabalin by ternary complexation using trapped ion mobility spectrometry

“…Due to their unique structures, CDs can act as host molecules to form stereoselective complexes with enantiomers. These complexes can be applied to distinguish enantiomers in many fields 29–33 …”

“…Unfortunately, pregabalin enantiomers were not recognized by TIMS-TOF MS (FigureS1, supporting information). Based on the literature,22,26,30,38,39 the addition of alkali or transition cations could greatly increase the separation efficiency of isomeric compounds, prompting us to enhance the resolution of pregabalin enantiomers by preparing the ternary complexes of CD with pregabalin enantiomers and alkali-earth cations.Thus, the Ca 2+ ternary complexes, including [α-CD + pregabalin + Ca − H] + , [β-CD + pregabalin + Ca − H] + , and [γ-CD + pregabalin + Ca − H] + , were analyzed by TIMS-MS TOF. The mobilograms are shown in Figure 4.…”

Separation of β-Amyloid Tryptic Peptide Species with Isomerized and Racemized l-Aspartic Residues with Ion Mobility in Structures for Lossless Ion Manipulations

“…We overcame the poor resolution of their doubly protonated, [M + 2H] 2+ , adducts by supplementing the electrospray buffer with sodium acetate, allowing all epimer sets to be baseline-resolved as their [M + H + Na] 2+ adducts following SLIM SUPER IM separations with a CRIMP step to provide improved detection. 41,42…”