Concurrent Quantitation of Ganciclovir, Its Valine-Valine and Glycine-Valine Diester Dipeptide Prodrugs in Ocular Matrices and Enzyme Degradations by QTRAP LC-MS/MS

摘要

Ganciclovir (GCV) is a synthetic analogue of 2'-deoxy-guanosine. It is the agent of choice for the treatment of cytomegalovirus in immunosuppressed patients. Absorption of GCV is very limited with low bioavailability and cause renal diseases due to its long unchanged elimination in the urine. Valganciclovir, valine-valine-ganciclovir and glycine-valine-ganciclovir prodrugs had improved oral bioavailability, lipophilicity, solubility, optimal physiological pH (7.4) and enzymatic stability (10-fold higher compared to GCV). This prodrug provides the therapeutic concentration of GCV at the site of action with lower dose administration comparable to that achieved with intravenous injection. We developed and validated a sensitive and selective LC-MS/MS method to evaluate matrix stabilities and enzymatic degradations of diester linked dipeptide prodrugs of GCV to anticipate the bioanalytical application.