Simultaneous estimation of ZY-19489 and its active metabolite ZY-20486 in human plasma using LC-MS/MS, a novel antimalarial compound.

Aim: ZY-19489 is a new antimalarial drug candidate and selective LC-MS/MS method was established for estimation of ZY-19489 and its metabolite in human plasma. Materials & methods: LLE was employed for extraction, mass spectrometric quantification performed using positive ionization mode and DCP-IMP was used as an internal standard. The chromatographic separation was achieved using mobile phase 5 mM ammonium formate in water and 0.1% v/v ammonia solution in methanol:acetonitrile (90:10% v/v) and column Agilent Zorbex Extended C18, 3.5 µm, 100 × 4.6 mm with a 6-min run time. Results: The calibration curve of ZY-19489 was linear over range 1-500 ng/ml and 2-200 ng/ml for metabolite. Assay was reproducible, selective and devoid of matrix effect. Conclusion: The validated assay was implemented for clinical sample analysis derived from healthy human subjects and parasitemia-induced subjects.

Efficacy and safety of pegylated interferon-α2b in moderate COVID-19: a phase 3, randomized, comparator-controlled, open-label study.

OBJECTIVE: To evaluate the efficacy and safety of pegylated interferon alpha-2b (PEG IFN-α2b) administered in conjunction with the standard of care (SOC) in subjects with moderate coronavirus disease-19 (COVID-19). METHODS: In this study, adult subjects with confirmed moderate COVID-19 were randomized in a 1:1 ratio to receive either PEG IFN-α2b + SOC or SOC alone. The primary endpoint was a two-point improvement in clinical status on Day 11, measured by the World Health Organization's seven-point ordinal scale. RESULTS: Of 250 subjects, 120 were randomized to the PEG IFN-α2b + SOC arm and 130 were randomized to the SOC arm. The results for the PEG IFN + SOC arms vs the SOC arm for the proportion of subjects with a two-point improvement in the seven-point ordinal scale were 80.36% vs 68.18% (P=0.037) on Day 8, 91.60% vs 92.56% (P=0.781) on Day 11, and 94.12% vs 95.93% (P=0.515) on Day 15. There was a time-dependent decrease in the biomarkers in both arms, and no clinically significant changes in laboratory parameters. The safety profile was similar in both arms. CONCLUSION: PEG IFN-α2b induced early viral clearance, improved the clinical status, and decreased the duration of supplemental oxygen. It provides a viable treatment option and can limit the spread of severe acute respiratory syndrome coronavirus-2.