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学科主题: 物理化学
题名: Simultaneous determination of five CYP probe drugs and their metabolites by quantitative cassette analysis using ultra-fast liquid chromatography/diode array detector
作者: Mao YX(毛玉玺) ;  Ge GB(葛广波) ;  Yang L(杨凌)
会议名称: The 24th International Symposium on Microscale Bioseparations
会议日期: 2009-10-19
出版日期: 2009-10-19
会议地点: 中国
其他题名: 基于超快速液相色谱/二极管阵裂管检测器采用盒式分析检测五个CYP探针底物及其代谢产物
通讯作者: Ling Yang
部门归属: 十八室
主办者: 大连化学物理研究所
摘要: A valid, efficient and time-saving cassette analytical method has been developed for simultaneous determination of five CYP probe drugs and their metabolites by using ultra-fast liquid chromatography coupled with diode array detector (UFLC-DAD). Chromatographic separation was performed with a Shim-pack XR-ODS column (75 mm × 2.0 mm, 2.2 µ), with the mobile phase consisted of methanol and 0.5% formic acid at the flow rate of 0.4 mL min-1. Five probe reactions for CYP isoforms including Phenacetin-O-deethylation (CYP1A2), Coumarin-7-hydroxylation (CYP2A6), Paclitaxel-6-hydroxylation (CYP2C8), Chlorzoxazone-6-hydroxylation (CYP2E1), Nifedipine oxidation (CYP3A4) were selected for this study. The detection wavelengths of five CYP probe reactions were set at the maximal absorbent wavelengths of Phenacetin, Coumarin, Paclitaxel, Chlorzoxazone and Nifedipine, were 245 nm, 320 nm, 230 nm, 280 nm and 250 nm, respectively. The limit of detection of Phenacetin, Coumarin, Paclitaxel, Chlorzoxazone, Nifedipine and their metabolites ranged from 0.08 to 0.25 ng. The linear detection range of Phenacetin, Coumarin, Paclitaxel, Chlorzoxazone, Nifedipine and their metabolites ranged from 0.8 to 200 ng with good correlation coefficient (>0.9998). The inter-day and intra-day reproducibility were evaluated and the results shown that the relative standard deviations (RSDs) of the retention times and peak areas were less than 2.1 % for the CYP probe drugs and their metabolites. All detected compounds could be isolated with satisfactory resolution within 16 minutes, and the method was successfully applied in rapid assessment and screening of different CYPs activities of human liver microsome from 15 individuals. The five samples for each probe reaction after 30 min incubation with human liver microsome and cofactors were pooled with equal volume, and then analyzed by UFLC-DAD. The conversion of each probe drug was determined to display the activity of the corresponding CYP isoform. The quantitative results from the cassette analysis procedure agreed well with those results obtained from conventional discrete LC analysis. The UFLC-based method offers a significant increase in analytical throughput and can be used in rapid assessment of different CYPs activities of animal liver microsomes from different species and individuals. Furthermore, the method also can be applied in rapid screening of inhibitors of each CYP isoform for drug-drug interaction related studies. The proposed cassette analysis method is rapid, more accurate and more acceptable than previously reported cocktail methods which were less accurate due to the existed competitive inhibitions from several probe substrates.
语种: 中文
内容类型: 会议论文
URI标识: http://cas-ir.dicp.ac.cn/handle/321008/113712
Appears in Collections:中国科学院大连化学物理研究所_会议论文

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Recommended Citation:
Mao YX,Ge GB,Yang L. Simultaneous determination of five CYP probe drugs and their metabolites by quantitative cassette analysis using ultra-fast liquid chromatography/diode array detector[C]. 见:The 24th International Symposium on Microscale Bioseparations. 中国. 2009-10-19.
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