ABSTRACT
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.
Subject(s)
Antiviral Agents/therapeutic use , Azithromycin/therapeutic use , COVID-19 Drug Treatment , Hydroxychloroquine/therapeutic use , SARS-CoV-2/pathogenicity , Anti-Bacterial Agents/therapeutic use , Antimalarials/therapeutic use , COVID-19/virology , Clinical Trials as Topic , Drug Combinations , Drug Repositioning , Humans , Indoles/therapeutic use , Interferon-alpha/therapeutic use , Lopinavir/therapeutic use , Ritonavir/therapeutic use , UncertaintyABSTRACT
To administer vitamin C (VC) with precision to patients with the coronavirus disease (COVID-19), we developed an ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to assess plasma VC concentrations. 31 patients with COVID-19 and 51 healthy volunteers were enrolled. VC stability was evaluated in blood, plasma, and precipitant-containing stabilizers. A proportion of 7.7 % of VC was degraded in blood at room temperature (RT) (approximately 20-25 °C) at 1.5 h post administration with respect to the proportion degraded at 0.5 h, but without statistical difference. VC was stable in plasma for 0.75 h at RT, 2 h at 4 °C, 5 days at -40 °C, and 4 h in precipitant-containing stabilizer (2 % oxalic acid) at RT. The mean plasma concentration of VC in patients with COVID-19 was 2.00 mg/L (0.5-4.90) (n = 8), which was almost 5-fold lower than that in healthy volunteers (9.23 mg/L (3.09. 35.30)) (n = 51). After high-dose VC treatment, the mean VC concentration increased to 13.46 mg/L (3.93. 34.70) (n = 36), higher than that in healthy volunteers, and was within the normal range (6-20 mg/L). In summary, we developed a simple UPLC-MS/MS method to quantify VC in plasma, and determined the duration for which the sample remained stable. VC levels in patients with COVID-19 were considerably low, and supplementation at 100 mg/kg/day is considered highly essential.