Development of a green and validated UHPLC-MS/MS method for assessing the pharmacokinetics and safety of PA-PEG12-PA in MCF-7 cells

Abstract

This study developed a UHPLC-MS/MS method to evaluate the cellular pharmacokinetics of α,ω-dipropionic acid polyethylene glycol (PA-PEG₁₂-PA) in MCF-7 cells. The findings revealed time-dependent cellular accumulation, with intracellular concentrations plateauing at 24 hours post-treatment. However, the overall uptake efficiency remained low, with only approximately 0.00066% of the administered dose internalized after 48 hours, indicative of limited passive membrane permeability attributed to the compound's high hydrophilicity. Importantly, PA-PEG₁₂-PA showed no significant cytotoxicity across a wide concentration range (3–3000 µg mL⁻¹), confirming its biocompatibility. The analytical method itself was validated as precise, accurate, and environmentally sustainable according to BAGI, AGREE, and GEMAM metrics. These results provide crucial insights into the cellular disposition of PA-PEG₁₂-PA, supporting its further investigation as a potential drug carrier.