Biological Sciences Division , Pacific Northwest National Laboratory , Richland , Washington 99352 , United States.
Anal Chem. 2018 Sep 18;90(18):11086-11091. doi: 10.1021/acs.analchem.8b02990. Epub 2018 Aug 24.
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.
胆汁酸（BAs）是一类重要的甾体代谢物，其水平变化通常与疾病状态和其他健康状况有关。目前对这些结构相似的化合物的分析受到灵敏度低和分离时间长的限制，且常常不能很好地实现异构体分离。为了克服这些挑战，并为 BA 异构体提供快速分析，我们利用环糊精加合物结合结构无损离子操控（SLIM）提供的新型离子淌度（IM）分离能力。研究发现，环糊精与牛磺酸和甘氨酸结合的 BA 异构体都相互作用，形成刚性的非共价主体-客体包合物。如果不使用环糊精加合物，BA 异构体在各自的淌度上几乎相同，因此无法进行基线分离。每个环糊精-胆汁酸主体-客体包合物的分离都在不到 1 秒的时间内完成，与当前基于液相色谱的分离相比，提供了一种更快的替代方法。SLIM 提供了积累更大离子群体和 IM 峰压缩的能力，从而实现了更高的分辨率分离，并增加了所研究 BA 异构体的信号强度。
