Liquid Chromatography‐Tandem Mass Spectrometry Analysis and Pharmacokinetics of Doxorubicin and Its Prodrug in Rats After Administration of Nanoparticles

ABSTRACT To further improve the dilemma facing the clinical application of doxorubicin (DOX), we designed a cathepsin B sensitive DOX prodrug albumin nanoparticle (NP). To evaluate the pharmacokinetics of prodrug albumin NPs (C16‐GFLG‐PAB‐DOX NPs), we developed and validated a liquid chromatography‐tandem mass spectrometry method for the same time analysis of DOX and its fatty acid prodrug (C16‐GFLG‐PAB‐DOX) in rat plasma. The method uses the precipitated protein method to extract analytes from rat plasma. The validated method on selectivity, linearity ( r ≥ 0.992), precision (relative standard deviation: 3.5%–9.5%), accuracy (relative error: −2.9% to 3.5%), extraction recovery (80.2% to 90.4%), matrix effect (87.8% to 96.6%), and stability in different conditions were satisfied. Therefore, the pharmacokinetic behavior of C16‐GFLG‐PAB‐DOX NPs in rats was investigated using this analytical approach. The outcome of the pharmacokinetic study illustrated that prodrug albumin NPs are promising to alleviate the problems associated with DOX in clinical applications.