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.