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A UPLC-MS/MS method for quantification of a novel doxorubicin conjugation prodrug in tumor cells
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Nan ZHENG1, Xing WANG2, Yao-qi WANG2, Guo-bing XU1, Hua ZHANG2, Wen-bing DAI2, Bing HE2, Qiang ZHANG2, Xue-qing WANG2, *
Acta Pharmaceutica Sinica | 2018, 53(2) : 278 - 283
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Acta Pharmaceutica Sinica | 2018, 53(2): 278-283
• ORIGINAL ARTICLES •
A UPLC-MS/MS method for quantification of a novel doxorubicin conjugation prodrug in tumor cells
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Nan ZHENG1, Xing WANG2, Yao-qi WANG2, Guo-bing XU1, Hua ZHANG2, Wen-bing DAI2, Bing HE2, Qiang ZHANG2, Xue-qing WANG2, *
Affiliations
  • 1. Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing), National Drug Clinical Trial Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
  • 2. Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Published: 2018-02-12 doi: 10.16438/j.0513-4870.2017-1031
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In this study, we developed a rapid and sensitive ultra high-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS) method to detect a sulfide bond doxorubicin conjugation prodrug (DOX-S-DOX) in human breast cancer tumor cells (MCF-7). The samples were prepared by acetonitrile precipitation using daunorubicin as internal standard (IS). A reversed phase C18 analytical column (Agilent Eclipse plus C18 RRHD 1.8 μm, 2.1 mm×50 mm) was utilized to separate the samples under gradient elution conditions. Mobile phase was a mixture of 0.1% formic acid in water and methanol at a flow rate of 0.4 mL ·min-1. The analysis was conducted on the mass spectrometer using an electrospray interface (ESI) in the positive ionization model. The calibration range was 20.0-400 ng·mL-1 with the correlation coefficients (r2) ≥ 0.99. The inter-and intra-assay precision (relative standard deviation, RSD%) of quality control samples was within 3.77%-8.35% and relative error (RE%) for accuracy was between -2.04% and 2.62%. Recovery (97.67%-104.2%) and matrix effect (104.8%-113.9%) were consistent, precise, and reproducible at different quality control levels in accordance with FDA guidance. The assay was successfully used in the cellular pharmacokinetics study of DOX-S-DOX, which may provide a clue to explore analytical methods of other prodrug forms of DOX.

doxorubicin prodrug  /  UPLC-MS/MS  /  cellular pharmacokinetic study
Nan ZHENG, Xing WANG, Yao-qi WANG, Guo-bing XU, Hua ZHANG, Wen-bing DAI, Bing HE, Qiang ZHANG, Xue-qing WANG. A UPLC-MS/MS method for quantification of a novel doxorubicin conjugation prodrug in tumor cells[J]. Acta Pharmaceutica Sinica, 2018 , 53 (2) : 278 -283 . DOI: 10.16438/j.0513-4870.2017-1031
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Article Info
doi: 10.16438/j.0513-4870.2017-1031
  • Receive Date：2017-10-19
  • Online Date：2026-01-15
  • Published：2018-02-12
Article Data
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History
  • Received：2017-10-19
  • Accepted：2017-12-04
Funding
Affiliations
    1. Key laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing), National Drug Clinical Trial Center, Peking University Cancer Hospital and Institute, Beijing 100142, China
    2. Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
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多孔菌科 Polyporaceae 8 14 6.70 蜡蘑属 Laccaria 5 2.39
红菇科 Russulaceae 3 23 11.00 小皮伞属 Marasmius 6 2.87
小菇属 Mycena 11 5.26
光柄菇属 Pluteus 5 2.39
红菇属 Russula 17 8.13
栓菌属 Trametes 5 2.39
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