Department of Chemistry, Mississippi State University, Mississippi State, Mississippi, USA.
J Mass Spectrom. 2023 Dec;58(12):e4985. doi: 10.1002/jms.4985.
Beta blockers are a class of drugs commonly used to treat heart-related diseases; they are also regulated under the World Anti-Doping Agency. Tandem mass spectrometry is often used in the pharmaceutical industry, clinical analysis laboratory, and antidoping laboratory for detection and characterization of drugs and their metabolites. A deeper chemical understanding of dissociation pathways may eventually lead to an improved ability to predict tandem mass spectra of compounds based strictly on their chemical structure (or vice versa), which is especially important for characterization of unknowns such as emerging designer drugs or novel metabolites. In addition to providing insights into dissociation pathways, the use of energy-resolved breakdown curves can produce improved selectivity and lend insights into optimal fragmentation conditions for liquid chromatography-tandem mass spectrometry LC-MS/MS workflows. Here, we perform energy-resolved collision cell and multistage ion trap collision-induced dissociation-mass spectrometry (CID-MS) experiments, along with complementary density functional theory calculations, on five beta blockers (acebutolol, atenolol, bisoprolol, carteolol, and labetalol), to better understand the details of the pathways giving rise to the observed MS/MS patterns. Results from this work are contextualized within previously reported literature on these compounds. New insights into the formation of the characteristic product ion m/z 116 and the pathway leading to characteristic loss of 77 u are highlighted. We also present comparisons of breakdown curves obtained via qToF, quadrupole ion trap, and in-source CID, allowing for differences between the data to be noted and providing a step toward allowing for improved selectivity of breakdown curves to be realized on simple instruments such as single quadrupoles or ion traps.
β受体阻滞剂是一类常用于治疗心脏相关疾病的药物；它们也受到世界反兴奋剂机构的监管。串联质谱通常用于制药行业、临床分析实验室和反兴奋剂实验室，用于检测和表征药物及其代谢物。对离解途径的更深入的化学理解最终可能导致能够根据化合物的化学结构（或反之亦然）严格预测串联质谱的能力得到提高，这对于表征未知物（如新兴的设计药物或新型代谢物）特别重要。除了提供对离解途径的深入了解外，使用能量分辨碎裂曲线还可以提高选择性，并深入了解液相色谱-串联质谱（LC-MS/MS）工作流程的最佳碎裂条件。在这里，我们对五种β受体阻滞剂（醋丁洛尔、阿替洛尔、比索洛尔、卡替洛尔和拉贝洛尔）进行了能量分辨碰撞池和多级离子阱碰撞诱导解离-质谱（CID-MS）实验，以及互补的密度泛函理论计算，以更好地了解导致观察到的 MS/MS 模式的途径的细节。这项工作的结果与这些化合物以前的文献报道相关联。突出了对产生特征性产物离子 m/z 116 的途径和导致特征性损失 77 u 的途径的新见解。我们还比较了通过 qToF、四极离子阱和源内 CID 获得的分解曲线，以便注意到数据之间的差异，并为在简单仪器（如单四极杆或离子阱）上实现更好的分解曲线选择性提供了一步。
