An automated streamlined method for the therapeutic drug monitoring of digoxin based on the online-solid-phase extraction liquid chromatography tandem high-resolution mass spectrometry.

Abstract

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 0.1-10ng mL-1 for digoxin with correlation coefficients of R2 > 0.999. The lower limit of quantitation (LLOQ) for digoxin was 0.1ng mL-1 . 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 10min 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.