A UPLC-MS/MS method for quantification of a novel doxorubicin conjugation prodrug in tumor cells
10.16438/j.0513-4870.2017-1031
- VernacularTitle:UPLC-MS/MS法分析新型多柔比星前药在肿瘤细胞中的浓度
- Author:
Nan ZHENG
1
;
Xing WANG
2
;
Yao-qi WANG
2
;
Guo-bing XU
1
;
Hua ZHANG
2
;
Wen-bing DAI
2
;
Bing HE
2
;
Qiang ZHANG
2
;
Xue-qing WANG
2
Author Information
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
- Publication Type:ORIGINAL ARTICLES
- Keywords:
doxorubicin prodrug;
UPLC-MS/MS;
cellular pharmacokinetic study
- From:
Acta Pharmaceutica Sinica
2018;53(2):278-283
- CountryChina
- Language:Chinese
-
Abstract:
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.
