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Journal of Chinese Pharmaceutical Sciences ›› 2016, Vol. 25 ›› Issue (8): 576-581.DOI: 10.5246/jcps.2016.08.064

• Original articles • Previous Articles     Next Articles

A simple and sensitive gradient elution liquid chromatography with tandem mass spectrometry (LC-MS/MS) method for the quantification of doxorubicin in rabbit plasma

Jialin Li1,2, Liying Guo1,2, Xiaoya Qin1,2, Tianyuan Fan1,2*   

  1. 1. State Key Laboratory of Natural and Biomimetic Drugs, Peking University Health Science Center, Beijing 100191, China
    2. Beijing Key Laboratory of Molecular Pharmaceutics and New Drug Delivery Systems, School of Pharmaceutical Sciences, Peking University Health Science Center, Beijing 100191, China
  • Received:2016-04-21 Revised:2016-05-10 Online:2016-09-01 Published:2016-05-15
  • Contact: Tel.: +86-010-82805123, E-mail: tianyuan_fan@bjmu.edu.cn
  • Supported by:
    National Natural Science Foundation of China (Grant No. 81473113).

Abstract:

In the present study, we developed and validated a simple and sensitive gradient elution liquid chromatography tandem mass spectrometry (LC-MS/MS) method for quantification of doxorubicin in rabbit plasma. Daunorubicin was used as an internal standard (IS). The doxorubicin and IS were extracted with ethyl acetate from plasma samples. The chromatographic separations were achieved on a C18 column (2.1 mm×50 mm, 2.5 μm) configured with a C18 guard column (2.1 mm×10 mm, 2.5 μm). The mobile phase of 0.1% formic acid-water solution and acetonitrile was delivered using a gradient elution program at a flow rate of 0.4 mL/min. The temperature for column was maintained at 40 ºC. The electrospray ionization (ESI) source was operated in the positive ion mode, and the quantification was conducted using multiple reaction monitoring (MRM) of the transitions m/z 544.07→396.96 and m/z 528.06→321.05 for doxorubicin and IS, respectively. The calibration curve of doxorubicin was linear (r > 0.999) within the range of 2-600 ng/mL. The lower limit of quantification was 2 ng/mL. The relative errors of intra­day and inter-day accuracies ranged from -2.48% to 0.18% and from -3.78% to 1.94%, respectively. The relative standard deviations of intra­day and inter-day precisions were less than 8.65% and 6.41%, respectively. The method exhibited satisfactory results in terms of specificity, sensitivity, matrix effect, recovery and stability. The newly developed LC-MS/MS method was reliable to monitor doxorubicin concentrations in rabbit plasma.

Key words: Doxorubicin, LC-MS/MS, Gradient elution, Rabbit plasma

CLC Number: 

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