质谱学报2017，Vol.38Issue(4)：460-467,8.DOI:10.7538/zpxb.2017.0035
LC-MS/MS法测定比格犬血浆中氯吡格雷活性代谢物
Determination of Clopidogrel Active Metabolite in Beagle Dog Plasma by LC-MS/MS
赵雪 1孙慧 1张琪 1任天明 1顾景凯1
作者信息
- 1. 吉林大学药物代谢研究中心,吉林 长春 130012
- 折叠
摘要
Abstract
A method of liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method was developed for determining clopidogrel active metabolite (AM) in beagle dog plasma.LC separation was performed using water containing 0.1% formic acid and acetonitrile as mobile phases with the gradient elution at a flow rate of 1 mL/min.Quantitative analysis was achieved after the chromatographic separation on an Ascentis C18 column (5 cm×4.6 mm×5 μm).The electrospray ionization (ESI) source in positive mode and multiple reaction monitoring (MRM) were used for the detection of clopidogrel AM derivative (MP-AM).The sample pretreatment conditions such as the extraction method, the derivative reagents were optimized.The alkylating reagent 2-bromo-3''-methoxyacetophenone (MPB) was used to stabilize clopidogrel AM in blood.Blood samples were centrifuged immediately after collection to take plasma and MPB was then added.Protein precipitation with iced acetonitrile (containing 0.1% formic acid) as precipitation solvent was used for sample extraction.The post-extracted samples were analyzed by LC-MS/MS.The peaks are narrow and symmetrical.The linear range of MP-AM is 1-1 000 μg/L, and the linear correlation coefficient is more than 0.995.The method has no matrix interference.The recoveries of MP-AM range from 92.8% to 95.1% at three spiked levels of 2.4, 24 and 800 μg/L with the relative standard deviations (RSD) less than 8.27% (n=6).The intra-assay/inter-assay accuracy and precision are all acceptable.The method is simple, accurate and robust, which is suitable for research the pharmacokinetic of AM in beagle dog plasma.关键词
氯吡格雷/活性代谢物/液相色谱-串联质谱(LC-MS/MS)/药代动力学Key words
clopidogrel/clopidogrel active metabolite/liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS)/pharmacokinetic分类
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赵雪,孙慧,张琪,任天明,顾景凯..LC-MS/MS法测定比格犬血浆中氯吡格雷活性代谢物[J].质谱学报,2017,38(4):460-467,8.
