The accurate and efficient measurement of small molecule disease markers for clinical diagnosis is of great importance. In this study, a quadrupole-linear ion trap (Q-LIT) tandem mass spectrometer was designed and built in our laboratory. Target precursor ions were first selected in the quadrupole, and then injected, trapped, and fragmented simultaneously in the linear ion trap (LIT) to reduce the space charge effect, enrich the target product ions, and promote sensitivity. The targeted analytes were measured with selected reaction monitoring using a positive scan mode with electrospray ionization (ESI). Ions with a mass-to-charge ratio (m/z) ranging from 195 to 2022 were demonstrated. When scanning at 1218 amu·s⁻¹, unit resolution and an accuracy of higher than m/z 0.28 was obtained for m/z up to 2000. The dimensionless Mathieu parameter (q) value used in this study was 0.40 for collision-induced dissociation (CID), which was activated by resonance excitation. And an overall CID efficiency of 64% was achieved (activation time, 50 ms). Guanidinoacetic acid (GAA) and creatine (CRE) were used as model compounds for small molecule clinical biomarkers. The limits of quantification were 1.0 and 0.2 nmol·L⁻¹ for GAA and CRE, respectively. A total of 77 actual samples were successfully analyzed by the home-built ESI-Q-LIT tandem mass spectrometry system. The developed method can reduce matrix interference, minimize space charge effects, and avoid the chromatographic separation of complex samples to simplify the pretreatment process. This novel Q-LIT system is expected to be a good candidate for the determination of biomarkers in clinical diagnosis and therapeutics.

小分子疾病标志物的准确高效测量对于临床诊断具有重要意义。在本研究中，我们实验室设计并建造了四极线性离子阱（Q-LIT）串联质谱仪。首先在四极杆中选择目标母离子，然后在线性离子阱 (LIT) 中同时进样、捕获和碎裂，以降低空间电荷效应，富集目标产物离子，提高灵敏度。使用带有电喷雾电离 (ESI) 的正扫描模式，通过选定的反应监测来测量目标分析物。展示了质荷比 ( m / z ) 范围为 195 至 2022 的离子。以 1218 amu·s ^-1扫描时, 单位分辨率和高于m/z 0.28的精度在m / z高达 2000 时获得。本研究中使用的无量纲 Mathieu 参数 ( q ) 值对于碰撞诱导解离 (CID) 为 0.40，其激活方式为共振激发。并且实现了 64% 的整体 CID 效率（激活时间，50 ms）。胍基乙酸 (GAA) 和肌酸 (CRE) 被用作小分子临床生物标志物的模型化合物。定量限为 1.0 和 0.2 nmol·L ^-1分别用于 GAA 和 CRE。自制的 ESI-Q-LIT 串联质谱系统共成功分析了 77 个实际样品。所开发的方法可以减少基质干扰，最大限度地减少空间电荷效应，避免复杂样品的色谱分离，从而简化预处理过程。这种新颖的 Q-LIT 系统有望成为临床诊断和治疗中确定生物标志物的良好候选者。