National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, People's Republic of China.
National Center for Organic Mass Spectrometry in Shanghai, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 345 Lingling Road, Shanghai 200032, People's Republic of China.
Anal Chim Acta. 2017 Apr 8;961:82-90. doi: 10.1016/j.aca.2017.01.036. Epub 2017 Jan 31.
The present work focused on the high-throughput screening and quantitation of guanidino compounds (GCs) and ureido compounds (UCs) in human thyroid tissues. The strategy employed benzylic rearrangement stable isotope labeling (BRSIL) for the sample preparation and then detection using liquid chromatography-drift tube ion mobility spectrometry-quadrupole time of flight mass spectrometry (LC-DTIMS-QTOF MS). A short reversed-phase LC realized an on-line desalting and a measurement cycle of 5.0 min. DTIMS separation enhanced the better specificity and selectivity for the benzil labeled GCs and UCs. The elevated mass resolution of QTOF MS enabled measure of the characteristic ions at accurate mass in MS and tandem MS spectra. Collision cross section (CCS) from DTIMS and accurate mass from QTOF MS were used as two qualifiers for the profiling and identification of GCs and UCs. In addition, an integral abundance arising from 3-D ion features (retention time, drift time, m/z) was applied to quantify the GCs and UCs in human thyroid tissues. The quantitative validation indicated good linearity (coefficient values ≥ 0.9981), good precision (1.0%-12.3% for intra-day and 0.9%-7.8% for inter-day) and good accuracy (91%-109%). The results demonstrated that the developed BRSIL coupled with LC-DTIMS-QTOF MS can be a powerful analysis platform to investigate GCs and UCs in human thyroid tissues.
本工作专注于高通量筛选和定量分析人甲状腺组织中的胍基化合物 (GCs) 和脲基化合物 (UCs)。该策略采用苄基重排稳定同位素标记 (BRSIL) 进行样品前处理，然后使用液相色谱-漂移管离子淌度谱-四极杆飞行时间质谱 (LC-DTIMS-QTOF MS) 进行检测。短的反相液相色谱实现了在线脱盐和 5.0 分钟的测量周期。DTIMS 分离增强了对苄基标记 GCs 和 UCs 的更好的特异性和选择性。QTOF MS 的高质量分辨率使我们能够在 MS 和串联 MS 谱中测量准确质量的特征离子。来自 DTIMS 的碰撞截面 (CCS) 和来自 QTOF MS 的准确质量被用作 GCs 和 UCs 分析和鉴定的两个定性指标。此外，还应用了 3-D 离子特征（保留时间、漂移时间、m/z）的积分丰度来定量分析人甲状腺组织中的 GCs 和 UCs。定量验证表明具有良好的线性（相关系数值≥0.9981）、良好的精密度（日内精度为 1.0%-12.3%，日间精度为 0.9%-7.8%）和良好的准确性（91%-109%）。结果表明，开发的 BRSIL 与 LC-DTIMS-QTOF MS 相结合可以成为研究人甲状腺组织中 GCs 和 UCs 的强大分析平台。
