Therapeutic Monitoring of Plasma Digoxin for COVID-19 Patients Using a Simple UPLC-MS/MS Method

Background: Cardiovascular diseases (CVD) have been reported in 8%-16% of patients with 2019 coronavirus disease (COVID-19). Digoxin is one of the main drugs to treat CVD. Objective: The clinician conducted therapeutic drug monitoring (TDM) of digoxin according to the drug usage on patients to monitor the concentration of digoxin, so as to avoid its toxic and side effects, and provide a theoretical reference for clinical usage of digoxin in patients with COVID-19. Methods: A method for quantifying digoxin concentration in plasma with ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) was developed. After simple protein precipitation of plasma with methanol, digoxin and its internal standard (digoxin-d3) were detected in the positive ion mode using multiple reaction monitoring. Results: Plasma digoxin in the range of 0.2 - 10 ng/mL had good linearity. The UPLC-MS/MS method was validated with inter-run accuracies ranging from 91.3% to 107.4% and precision less than 13%. Nine plasma samples (5 at valley concentration and 4 at follow-up after stopping dosing) from three patients with COVID-19 were tested. The mean plasma digoxin concentration was 0.73 ng/mL (ranged from 0 to 1.31 ng/mL). Digoxin was detected at the concentration of 0.93 ng/mL after stopping drug administration for 14 days. Conclusion: In this study, we established a simple UPLC-MS/MS method using protein-precipitation to perform TDM of digoxin in patients with COVID-19, and found that about 56% of digoxin plasma concentration was within the treatment window (0.8 - 2.0 ng/mL). Digoxin can be remained in the body for nearly 14 days in severe patients with COVID-19 after stopping dosing.