College of Chemistry and Pharmaceutical Sciences, Qingdao Agricultural University, Qingdao, China.
Department of Integrated of Chinese and Western Medicine, The Affiliated Yantai Yuhuangding Hospital of Qingdao University Medical College, Yantai, China.
Rapid Commun Mass Spectrom. 2021 Nov 30;35(22):e9191. doi: 10.1002/rcm.9191.
Digoxin is widely used in the clinical treatment of cardiovascular diseases. However, due to its extremely narrow therapeutic window, therapeutic drug monitoring (TDM) is vitally important. In consideration of the time-consuming and labor-intensive nature of the traditional techniques, an automated and efficient method was required for the clinical individualized TDM of digoxin.
An online solid-phase extraction liquid chromatography tandem high-resolution mass spectrometry (online-SPE-LC-HRMS) method was developed and applied for the determination of digoxin in plasma. The online SPE-LC steps included pretreatment and separation of plasma samples that were carried out using a Waters Oasis HLB cartridge and XBridge Shield RP18 column, respectively. A high-resolution Q Orbitrap mass spectrometer with targeted-selected ion monitoring in negative scan mode was applied to monitor formate-adduct ions [M + HCOO] m/z 825.42781 for digoxin.
Linearity was shown over the range 0.1-10 ng mL for digoxin with correlation coefficients of R > 0.999. The lower limit of quantitation (LLOQ) for digoxin was 0.1 ng mL . Extraction recoveries ranged from 82.61% to 94.28% for digoxin. The intra- and inter-day precision values were < 5.53% with accuracy ranging from 84.97% to 96.75%. The total running time was 10 min for each sample.
The established method displayed satisfactory recoveries, accuracy, precision, and stability, and successfully applied on the TDM of digoxin. This automated streamlined method provides a powerful tool to guide the individualized administration of digoxin, which is significant for the practice of precision medicine.
地高辛被广泛应用于心血管疾病的临床治疗中。然而，由于其治疗窗极窄，治疗药物监测（TDM）至关重要。考虑到传统技术耗时且费力，需要一种自动化且高效的方法来进行地高辛的临床个体化 TDM。
开发并应用了一种在线固相萃取液相色谱串联高分辨率质谱（online-SPE-LC-HRMS）方法来测定血浆中的地高辛。online-SPE-LC 步骤包括预处理和血浆样品分离，分别使用 Waters Oasis HLB 萃取小柱和 XBridge Shield RP18 色谱柱进行。采用带靶向选择离子监测的高分辨率 Q Orbitrap 质谱仪，以负扫描模式监测甲酸加合离子 [M + HCOO] m/z 825.42781 作为地高辛的监测离子。
地高辛在 0.1-10ng·mL 范围内呈线性，相关系数 R > 0.999。地高辛的定量下限（LLOQ）为 0.1ng·mL 。地高辛的提取回收率在 82.61%至 94.28%之间。日内和日间精密度值均<5.53%，准确度在 84.97%至 96.75%之间。每个样品的总运行时间为 10 分钟。
该方法显示出满意的回收率、准确度、精密度和稳定性，成功应用于地高辛的 TDM。这种自动化简化的方法为指导地高辛的个体化给药提供了有力工具，对精准医学的实践具有重要意义。
