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Improved HPLC method for doxorubicin quantification in rat plasma to study the pharmacokinetics of micelle‐encapsulated and liposome‐encapsulated doxorubicin formulations
Author(s) -
Wei Guangli,
Xiao Shuhua,
Si Duanyun,
Liu Changxiao
Publication year - 2008
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.1054
Subject(s) - chemistry , chromatography , doxorubicin , protein precipitation , detection limit , micelle , pharmacokinetics , liposome , high performance liquid chromatography , formic acid , aqueous solution , pharmacology , biochemistry , medicine , surgery , chemotherapy
An improved simple, rapid and accurate HPLC method for quantification of doxorubicin derived from micelle‐encapsulated or liposome‐encapsulated doxorubicin formulation in rat plasma was described. The mobile phase consisting of a mixture of methanol–water [containing 0.1% formic acid anhydrous and 0.1% ammonia solution (25%), pH 3.0], 60:40, was delivered at a flow rate of 1.0 mL/min. Sample preparation for micelle‐ or liposome‐encapsulated doxorubicin in rat plasma were achieved directly by protein precipitation with acetonitrile. Doxorubicin and daunorubicin (internal standard, IS) were separated on a C 18 reversed‐phase HPLC column and quantified by a fluoresence detection with an excitation wavelength of 475 nm and an emission wavelength of 580 nm. The linearity was obtained over the range of 5.0–1000.0 ng/mL and 1.0–200.0 µg/mL for doxorubicin and the lower limit of quantitation was 5.0 ng/mL. For each level of quality control samples, inter‐ and intra‐assay precision was less than 9.6 and 5.1% (relative standard deviation), respectively, and percentage error was within ±2.6%. The extraction recoveries of doxorubicin in the range of 10 ng/mL to 100 µg/mL in rat plasma were between 94.1 and 105.6%. This method was successfully applied to the pharmacokinetic study of doxorubicin formulations after i.v. administration to rats. Copyright © 2008 John Wiley & Sons, Ltd.