A combined assay for quantifying remdesivir and its metabolite, along with dexamethasone, in serum

Reckers, Andrew; Wu, Alan H B; Ong, Chui Mei; Gandhi, Monica; Metcalfe, John; Gerona, Roy

BACKGROUND: As global confirmed cases and deaths from coronavirus disease 2019 (COVID-19) surpass 100 and 2.2 million, respectively, quantifying the effects of the widespread treatment of remdesivir (GS-5734, Veklury) and the steroid dexamethasone is becoming increasingly important. Limited pharmacokinetic studies indicate that remdesivir concentrations in serum decrease quickly after dosing, so its primary serum metabolite GS-441524 may have more analytical utility. OBJECTIVES: We developed and validated a method to quantify remdesivir, its metabolite GS-441524 and dexamethasone in human serum. METHODS: We used LC-MS/MS and applied the method to 23 serum samples from seven patients with severe COVID-19. RESULTS: The method has limits of detection of 0.0375 ng/mL for remdesivir, 0.375 ng/mL for GS-441524 and 3.75 ng/mL for dexamethasone. We found low intra-patient variability, but significant inter-patient variability, in remdesivir, GS-441524 and dexamethasone levels. CONCLUSIONS: The significant inter-patient variability highlights the importance of therapeutic drug monitoring of COVID-19 patients and possible dose adjustment to achieve efficacy.