Rapid sensitive bioscreening of remdesivir in COVID-19 medication: Selective drug determination in the presence of six co-administered therapeutics

Abstract

The widespread coronavirus 2019 (COVID-19) pandemic, attributed to the severe acute respiratory syndrome coronavirus-2, has resulted in global lockdowns and excess mortality. Remdesivir (RM) is the first and only antiviral drug that the US Food and Drug Administration (FDA) has approved so far for COVID-19. The treatment protocol involves multidrug combinations, basically depending on RM, in addition to antimicrobials, antipyretics, corticosteroids, and anticoagulants. This study develops and validates sensitive and selective RM screening in spiked human plasma in the presence of commonly co-administered drugs. Hydroxychloroquine, azithromycin, paracetamol, dexamethasone, and anticoagulants (rivaroxaban and edoxaban) have been detected simultaneously with RM in the same biological matrix. Separation has been efficiently achieved by simple reversed phase HPLC with dual detectors. Diode array detector and fluorimetric detection have been used to compare their sensitivity and selectivity. Both assays have been validated according to bioanalytical FDA validation parameters. Chromatographic separation and quantitation of RM along with concomitant drugs instantly bioscreen COVID-19 multiple therapy medication in 10 min run time. Furthermore, the proposed in vitro study takes the lead for prospective testing of possible drug–drug interactions that alter the pharmacokinetic profiles of drugs.

Keywords

• remdesivir
• sars-cov-2
• combination therapy
• human plasma
• hplc-dad
• hplc-fd