Tandem mass spectrometry of small-molecule antiviral drugs: 3. antiviral agents against herpes, influenza and other viral infections

For the treatment of various viral infections, antiviral drugs may be used. Liquid chromatography–mass spectrometry (LC–MS) with tandem mass spectrometry (MS–MS) operated in selected-reaction monitoring (SRM) mode is the method of choice in quantitative bioanalysis of drugs, e.g., to establish bioavailability, to study pharmacokinetics, and later on possibly for therapeutic drug monitoring. In this study, the fragmentation in MS–MS of small-molecule antiviral drugs against herpes and influenza viruses is reviewed. In this way, insight is gained on the identity of the product ions used in SRM. Fragmentation schemes of antiviral agents are also relevant in the identification of drug metabolites or (forced) degradation products. As information of the fragmentation of antiviral drugs in MS–MS and the identity of the product ions is very much scattered in the scientific literature, it was decided to collect this information and to review it. In this third study, attention is paid to small-molecule antiviral agents used against herpes and influenza virus infections. In addition, some attention is paid to broad-spectrum antiviral agents, that are investigated with respect to their efficacy in challenging virus infections of this century, e.g., involving Ebola, Zika and corona viruses, like SARS-CoV-2, which is causing a world-wide pandemic at this very moment. The review provides fragmentation schemes of ca. 35 antiviral agents. The identity of the product ions used in SRM, i.e., elemental composition and exact-m/z, is tabulated, and more detailed fragmentation schemes are provided.