The conjugation of drugs to target therapeutics has become a promising method that could improve the efficacy of therapy and reduce side effects. Herein, we describe the efforts to covalently link the anti-lymphoma agent dasatinib to the truncated aptamer Sgc8-c, expecting the new hybrids to specifically damage lymphoma cells but with minimal toxicity towards non-target cells. Two linkages, ester and carbamate, with variable pH labilities were used to connect Sgc8-c with dasatinib. Different reaction conditions were studied by varying the solvent, time, temperature, heat source, pH and counter-ions. Each product from the reaction mixture was analysed by qualitative electrospray ionization time-of-flight mass spectrometry, identifying the nucleic acid modifications formed under the different experimental conditions. Among the reactions, depurinations from the 3-extreme mainly occurred as lateral processes. Preparation of the carbamate-linked Sgc8-c–dasatinib hybrid Sgc8-c-carb-da was successful but the ester-linked hybrid only produced lateral undesired products. The potential biotherapeutic Sgc8-c-carb-da displayed the ability to trigger dasatinib at endosomal pH, which is optimal because this could be the aptamer’s cellular uptake route.