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

(E-pub Ahead of Print)

Author(s): Yaru Xing, Lin Yin, Mingquan Guo, Huichun Shi, Tangkai Qi, Lin Wang, Ziqing Kong, Yingying Li, Pengyun Liu, Hongzhou Lu*, Lijun Zhang*

Journal Name: Current Pharmaceutical Analysis

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Background: Cardiovascular diseases (CVD) were reported in 8% - 16% of patients with 2019 coronavirus disease (COVID-19). Digoxin was one of the main drugs to treat CVD.

Objective: The clinician applied for therapeutic drug monitoring (TDM) of digoxin according to the drug usage of the patients to monitor their 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 a simple protein precipitation of plasma with methanol, digoxin and its internal standard (digoxin-d3) were detected in positive ion mode using multiple reaction monitoring .Results: Plasma digoxin in the range of 0.2 - 10 ng/mL had a good linearity. The UPLC-MS/MS method was validated with inter-run accuracies from 91.3% to 107.4% and precisions 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.

Keywords: COVID-19, cardiovascular diseases, digoxin, UPLC-MS/MS, plasma, therapeutic drug monitoring.

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(E-pub Ahead of Print)
DOI: 10.2174/1573412917999201102205715
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