Simultaneous determination of doxorubicin and its dipeptide prodrug in mice plasma by HPLC with fluorescence detection.

Journal: Journal of pharmaceutical analysis
Published Date:

Abstract

A simple and sensitive high performance liquid chromatography with fluorescence detection (HPLC-FD) has been developed for simultaneous quantification of doxorubicin (DOX) and its dipeptide conjugate prodrug (PDOX) in mice plasma. The chromatographic separation was carried out on an Amethyst C-H column with gradient mobile phase of 0.1% formic acid and 0.1% formic acid in acetonitrile at a flow rate of 1.0 mL/min. The excitation and emission wavelengths were set at 490 and 550 nm, respectively. The method was comprehensively validated. The limits of detection were low up to 5.0 ng/mL for DOX and 25.0 ng/mL for PDOX. And the limits of quantification were low up to 12.5 ng/mL for DOX and 50 ng/mL for PDOX, which were lower than those for most of the current methods. The calibration curves showed good linearity (>0.999) over the concentration ranges. The extraction recoveries ranged from 84.0% to 88.2% for DOX and from 85.4% to 89.2% for PDOX. Satisfactory intra-day and inter-day precisions were achieved with RSDs less than 9.1%. The results show that the developed HPLC-FD method is accurate, reliable and will be helpful for preclinical pharmacokinetic study of DOX and PDOX.

Authors

  • Jing Han
    Key Laboratory of Combinatorial Biosynthesis and Drug Discovery (Wuhan University), Ministry of Education; School of Pharmaceutical Sciences, Wuhan University, Wuhan 430071, China.
  • Jue Zhang
    Wuhan University Zhongnan Hospital, Wuhan 430071, China.
  • Haiyan Zhao
    Key Laboratory for Colloid and Interface Chemistry of Education Ministry, School of Chemistry and Chemical Engineering, Shandong University, 250100 Jinan, PR China.
  • Yan Li
    Interdisciplinary Research Center for Biology and Chemistry, Liaoning Normal University, Dalian, China.
  • Zilin Chen
    Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University, Ministry of Education, Wuhan University School of Pharmaceutical Sciences, Wuhan, 430071, China. Electronic address: chenzl@whu.edu.cn.

Keywords

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