Tandem mass spectrometry of small-molecule antiviral drugs: 2. hepatitis-related antivirals

Antiviral drugs are a class of compounds developed specifically for the treatment of viral infections. Quantitative analysis of antiviral drugs in biological matrix is important, e.g., to establish bioavailability, to study pharmacokinetics, and later on possibly for therapeutic drug monitoring. 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. The product ions that are selected for SRM are preferably structure specific. Therefore, it is important to understand the identity of these product ions. 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. This is not only relevant in SRM, but also in other studies, e.g., in the identification of drug metabolites or (forced) degradation products. In this second study, attention is paid to small-molecule antiviral agents used against hepatitis B and C virus infections. The review provides fragmentation schemes of ca. 25 antiviral agents, including some of their pharmacologically active metabolites. 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.