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An efficient extraction of doxorubicin (Dox) from homemade stealth hyalurionic acid (HA)-based nanoparticles (NPs) in rat plasma could not be performed by previously published methods. Therefore, we attempted to establish the novel NPs-breaking and UPLC–MS-MS method for evaluating the pharmacokinetic profiles of the homemade stealth HA NPs in rats. The pretreatment method of plasma samples used the liquid–liquid extraction method with isopropyl alcohol as NPs-breaking and protein-precipitating solvents, and the NPs-breaking efficiency of isopropyl alcohol was as high as 97.2%. The analyte and gliclazide (internal standard) were extracted from plasma samples with isopropyl alcohol and were separated on UPLC BEH C 18  with a mobile phase consisting of methanol and water (containing 0.1% formic acid). The method demonstrated good linearity at the concentrations ranging from 5 to 5,000 ng/mL. The intra- and interday relative standard deviations were &gt;10%. Finally, the method was successfully applied to a pharmacokinetic study of homemade stealth HA-based NPs in rats following intravenous administration.

journal of chromatographic science

Determination of Doxorubicin in Stealth Hyalurionic Acid-Based Nanoparticles in Rat Plasma by the Liquid–Liquid Nanoparticles-Breaking Extraction Method: Application to a Pharmacokinetic Study