Quality assessment and characterization of unregulated antiviral drugs for feline infectious peritonitis: implications for treatment, safety, and efficacy.

OBJECTIVE: Feline infectious peritonitis is fatal, and due to lack of approved treatments, unregulated antiviral drugs are used to treat this disease. This study set out to determine the purity of various batches of these drugs from several companies, characterize them, and note any impurities or other unusual characteristics. We also developed a method to qualitatively assess the primary components before administration.

SAMPLES: We tested 30 vials from 17 brands of GS-441524 and 5 vials from 1 brand of GC376. We compared the GS-441524 to a control standard from Ambeed and the GC376 to a standard from Cayman Chemical.

METHODS: We recorded physical appearance, pH, absorbance, HPLC retention times, and thin-layer chromatography retention factors for all of the samples. Some samples were used for nuclear magnetic resonance and mass spectrometric analysis.

RESULTS: Some of the GS-441524 vials were 10% to 25% more concentrated than advertised, but most of the GS-441524 samples tested were similar in purity and composition, both between batches and between brands. We also tested 5 vials of GC376 and found that 1 of the 5 vials contained GS-441524 rather than GC376 and the other 4 vials contained molnupiravir.

CLINICAL RELEVANCE: While all of the GS-441524 vials contained GS-441524, none of the GC376 vials tested contained GC376. GC376 is used in cats that are unresponsive to GS-441524, and use of the wrong antiviral can cause serious side effects. We provide suggested methods for distinguishing one drug from the other in new batches.