Pharmacokinetics of a liposomal formulation of doxorubicin in rats

Background: Measuring free drug concentration following systemic administration of a liposomal drug is a crucial aspect of the assessment of its in vivo behavior. Therefore we require an efficient method to separate free drug in the plasma from encapsulated drug. Objectives: To study the pharmacokin...

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Main Authors: Zongyu Liu (Author), Ye Bi (Author), Yating Sun (Author), Fei Hao (Author), Jiahui Lu (Author), Qingfan Meng (Author), Robert J. Lee (Author), Yaping Tian (Author), Jing Xie (Author)
Format: Book
Published: Elsevier, 2017-05-01T00:00:00Z.
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Summary:Background: Measuring free drug concentration following systemic administration of a liposomal drug is a crucial aspect of the assessment of its in vivo behavior. Therefore we require an efficient method to separate free drug in the plasma from encapsulated drug. Objectives: To study the pharmacokinetics of free doxorubicin (DOX) released from liposomal doxorubicin (L-DOX) in rats. Methods: L-DOX was prepared with encapsulation efficiency of 90% and was injected intravenously into rats. A solid-phase extraction (SPE) method coupled with UPLC-MS/MS was used to measure the concentration of F-DOX in rat plasma without disrupting the integrity of L-DOX. Results: This method exhibited a linear range of F-DOX from 0.2 to 200 ng/mL. Recovery, precision, linearity and accuracy of this technique appear satisfactory for pharmacokinetic study. The constituents of F-DOX ranged from 5.35% to 14.09% of total DOX in plasma at each time point measured after L-DOX administration. Conclusion: SPE method was suitable for studying the pharmacokinetics of F-DOX in rats receiving L-DOX. Keywords: Pharmacokinetics, Doxorubicin, Liposomes, Solid-phase extraction
Item Description:1319-0164
10.1016/j.jsps.2017.04.019