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

Author(s):

Yaru Xing, Lin Yin, Mingquan Guo, Huichun Shi, Tangkai Qi, Lin Wang, Ziqing Kong, Yingying Li, Pengyun Liu, Hongzhou Lu* and Lijun Zhang*   Pages 1 - 9 ( 9 )

Abstract:


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.

Affiliation:

Guilin Medical University, Guangxi 541004,, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508,, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508,, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508,, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508,, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508,, Hangzhou Calibra Diagnostics, LTD, Zhejiang 310030,, Guilin Medical University, Guangxi 541004,, Hangzhou Calibra Diagnostics, LTD, Zhejiang 310030,, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508,, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201508



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