Abstract：
Mass spectrometric analysis of non-volatile salts containing samples remains challenging due to salt-induced ion suppression and contamination. This challenge is even more pronounced for a liquid chromatography-mass spectrometry analysis, where the accumulation of salts in the transmission system poses an ongoing problem. In this study, a novel thermal assisted recrystallization ionization mass spectrometry (TARI-MS) device was developed to achieve efficient on-line desalting and prolonged analysis of saline samples. The core component of this device was a heated plate positioned between the electrospray unit and the MS inlet. The desalting mechanism was demonstrated as the spontaneous separation of target molecules from salts during the \"crystallization\" process. After optimization, the angle between the nebulizer and the heated plate was 45°; the distance between the front end of the heated plate and the MS inlet was 2 mm; the distance between the front edge of the heated plate and the center of the sample spray projected onto the heating plate was 3 mm; the distance between the emitter of nebulizer and the heated plate was 3 mm. TARI-MS realized direct analysis of eight drugs dissolved in eight commonly used non-volatile salts solutions (up to 0.5 mol/L). The high sensitivity, repeatability, linearity, accuracy, and intra- and inter-day precision of TARI-MS confirm its reliability as a robust tool for the analysis of saline samples. Furthermore, TARI-MS allowed continuous analysis of salty eluates of LC for up to nearly 1 h without maintenance and verified the feasibility of LC-MS analysis through detecting a five-drug mixture and a crude aripiprazole product. Finally, six impurities in the crude aripiprazole product were successfully detected by LC-TARI-MS. The established method holds promise for applications across academic and pharmaceutical domains.
摘要：
由于盐诱导的离子抑制和污染,含有非挥发性盐的样品的质谱分析仍然具有挑战性。对于液相色谱-质谱分析，这一挑战更加明显。在传输系统中盐分的积累带来了一个持续的问题。在这项研究中,开发了一种新型的热辅助重结晶电离质谱（TARI-MS）装置，以实现高效的在线脱盐和盐水样品的长期分析。该装置的核心部件是位于电喷雾单元和MS入口之间的加热板。脱盐机理被证明是在“结晶”过程中目标分子与盐的自发分离。优化后,雾化器与加热板之间的角度为45°;加热板的前端与MS入口之间的距离为2mm;加热板的前边缘与投射到加热板上的样品喷雾的中心之间的距离为3mm;雾化器的发射器与加热板之间的距离为3mm。TARI-MS实现了对8种常用非挥发性盐溶液（最高0.5mol/L）中溶解的8种药物的直接分析。高灵敏度，重复性,线性度准确度,TARI-MS的日间和日间精度证实了其作为盐水样品分析的强大工具的可靠性。此外，TARI-MS允许在不进行维护的情况下连续分析LC的含盐洗脱液多达1小时，并通过检测五种药物混合物和阿立哌唑粗品验证了LC-MS分析的可行性。最后,LC-TARI-MS成功检测到阿立哌唑粗品中的六种杂质。所建立的方法有望在学术和制药领域应用。
