title: 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.
abstract: 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 C18 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 >10%. Finally, the method was successfully applied to a pharmacokinetic study of homemade stealth HA-based NPs in rats following intravenous administration.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Xiaopeng
authors.initials: X
authors.lastname: Han
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Zhong
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Cong
authors.initials: C
authors.lastname: Luo
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Chunnuan
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China.
authors.forename: Qikun
authors.initials: Q
authors.lastname: Jiang
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, China sunjin66@21cn.com.
authors.forename: Jin
authors.initials: J
authors.lastname: Sun
mesh_terms: D000818:Animals; D001774:Blood Chemical Analysis / Q000379:methods*; D002851:Chromatography, High Pressure Liquid; D004317:Doxorubicin / Q000097:blood* / Q000493:pharmacokinetics*; D059625:Liquid-Liquid Extraction; D053758:Nanoparticles / Q000737:chemistry*; D010599:Pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry
chemical_list: D004317:Doxorubicin