The nonspecific sorption of hydrophobic pharmaceuticals on reaction vessel surfaces raises serious analytical challenges for their accurate quantification. Systematic error due to sorptive loss of analytes may result in significant overestimation of drug loading on nanomaterial-based Drug Delivery Systems (DDS), leading to inaccurate determinations of dosage and DDS efficiency. We evaluated sorptive losses of doxorubicin (DOX), an effective chemotherapeutic, in polystyrene based 96-well plates, and proposed a simple but effective method to prevent the nonspecific sorption of DOX using trace concentrations of polyethylene glycol (PEG). Relative to widely used proteinaceous and surfactant surface blocking agents, PEG is effective, easy to use, and does not interfere with drug loading to the DDS.