Methoxy poly (ethylene glycol)-poly(D, L-lactic acid) (mPEG-PDLLA) is a biocompatible and amphiphilic diblock copolymer composed of a hydrophilic poly(ethylene glycol) block and a hydrophobic poly(D, L-lactic acid) block, which can self-assemble into micelles in aqueous solution. It is one of the most widely used diblock copolymers for drug delivery, drug solubilization and drug encapsulation. Fully characterizing the in vivo fate of mPEG-PDLLA diblock copolymers is important to promote the further development of polymer-based nanocarrier drug delivery systems. However, to date, a bioanalysis assay for simultaneous quantification of mPEG-PDLLA and mPEG has not been reported. In this study, we developed such a novel LC-MS/MS assay based on CID in source technique and used it to study the multiple-dose pharmacokinetic, tissue distribution and excretion of mPEG2000-PDLLA2500-COOH and mPEG2000 in rat after intravenous administration. The results indicate that mPEG2000-PDLLA2500-COOH and mPEG2000 are mainly distributed to the liver, lung, spleen and kidney after intravenous administration. mPEG2000-PDLLA2500-COOH is mostly excreted via the renal route in the form of mPEG2000. Overall, the results of this study provide a comprehensive and clear picture of the in vivo fate of mPEG2000-PDLLA2500-COOH which will be useful in evaluating the efficiency and safety of polymer-based nanocarrier drug delivery systems.
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