期刊
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
卷 879, 期 21, 页码 1967-1972出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.jchromb.2011.05.031
关键词
Vincristine; HPLC; Pharmacokinetics; PLGA-PEG; Nanoparticle
资金
- National Natural Science Foundation of China [30973644]
- National Basic Research Program of China (973 Program) [2007CB936004]
- National comprehensive technology platforms for innovative drug (RD) [2009ZX09301-007]
- Key Projects of National New Drug [2009ZX09502-009]
The aim of this study is to develop a simple and applicable HPLC method for the detection of vincristine in rat plasma after administration of poly(lactic-co-glycolic acid)-poly(ethylene glycol) (PLGA-PEG) nanoparticles loaded with vincristine sulfate (VCR). Vincristine was extracted from rat plasma and vinblastine sulfate was chosen as the internal standard (IS). Chromatographic separation of VCR and IS was achieved by a Dikma Dimonsil C-18 column (200 mm x 4.6 mm) with the mobile phase consisting of 0.02 M sodium dihydrogen phosphate-methanol (36:64, v/v, pH = 4.7) at a flow rate of 1.0 mL/min. The ultraviolet detection wavelength was set at 276 nm. The calibration curve was linear over a concentration range of 0.05-5.0 mu g/mL. The intra-day and inter-day accuracy for three quality controls (QC) samples was 93.48-107.74% and 92.61-96.58%, respectively; the precision was less than 9%. The average method recoveries for vincristine from spiked plasma at all QC levels were over 83%; and extraction recoveries were between 66 and 70%. Vincristine was stable in rat plasma for one month at -80 degrees C, for 8 h at room temperature, as well as during three freeze-thaw cycles. This HPLC method was applied successfully to the pharmacokinetic study of vincristine in rats after a single intravenous injection of VCR in physiological saline (F-VCR) solution, VCR-loaded PLGA-mPEG nanoparticles with (NP1) and PLGA-PEG-folate nanoparticles (NP2) suspension, respectively. There were significant differences in main pharmacokinetic parameters between F-VCR and the nanoparticles. Both kinds of VCR-loaded nanoparticles displayed improved pharmacokinetic profiles. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.
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