中国中药杂志

2013, v.38(19) 3363-3367

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UPLC-MS/MS测定青蒿素代谢抑制剂猫眼草黄素及大鼠血浆药代动力学研究
Determination of chrysosplenetin,metabolic inhibitor of artemisinin,in rat plasma by UPLC-MS /MS and study on its pharmacokinetics

陈靖;纪红燕;魏世杰;付雪艳;刘梦英;吴秀丽;
CHEN Jing;JI Hong-yan;WEI Shi-jie;FU Xue-yan;LIU Meng-ying;WU Xiu-li;School of Pharmacy,Ningxia Medical University;Institute of Clinical Pharmacology,General Hospital of Ningxia Medical University;

摘要(Abstract):

目的:建立UPLC-MS/MS测定大鼠血浆中青蒿素代谢抑制剂猫眼草黄素(chrysosplenetin,CHR)的体内分析方法,并考察其药代动力学参数。方法:血浆样品以乙腈沉淀蛋白;采用Shim-pack XR-ODS C18色谱柱(2.0 mm×100 mm,2.2μm),以地西泮为内标,流动相为甲醇-0.1%甲酸水溶液(87∶13);质谱条件为电喷雾离子源(ESI源),正离子模式检测;样品分析时间为2 min。结果:CHR在5~5 000μg·L-1线性良好(r=0.999 3),提取回收率为69.0%~81.2%,日内、日间精密度和准确度符合要求。CHR口服吸收差,存在双峰甚至多峰现象;静脉注射消除半衰期短,低、中、高剂量组t1/2分别为(17.01±8.06),(24.62±4.59),(28.46±4.63)min。结论:该方法特异、快速、灵敏,可用于CHR药代动力学分析。
Objective: The study aimed to develop the assay of chrysosplenetin( CHR),a metabolic inhibitor of artemisinin by UPLC-MS / MS in rat plasma and investigate the pharmacokinetics parameters of CHR. Method: The plasma samples were precipitated by acetonitrile to remove the proteins. Separation was carried out on a Shim-pack XR-ODS C18( 2. 0 mm ×100 mm,2. 2 μm) column using a mobile phase containing methanol-0. 1% formic acid( 87∶ 13) using by diazepam as internal standard. Mass spectrometer with electrospray ionization( ESI) operated in the positive ion mode was used for analysis. Total analysis time was 2 min. Result: The assay was linear in the range 5-5 000 μg·L- 1( r =0. 999 3) with recoveries in the range from 69. 0% to 81. 2% and satisfied inter-,intra- precision and accuracy. CHR after oral administration is not easy to absorb with double or multimodal peak phenomenon. The t1 /2of CHR after intravenous injection was very short and that of low,medium,and high dosage was( 17. 01 ± 8. 06),( 24. 62 ± 4. 59),( 28. 46 ±4. 63) min,respectively. Conclusion: The developed method was special,rapid,and sensitive for determination of CHR pharmacokinetics.

关键词(KeyWords): UPLC-MS/MS;猫眼草黄素;药代动力学;血浆;大鼠
UPLC-MS/MS;chrysosplenetin;pharmacokinetics;plasma;rat

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基金项目(Foundation): 国家自然科学基金项目(30960465)

作者(Author): 陈靖;纪红燕;魏世杰;付雪艳;刘梦英;吴秀丽;
CHEN Jing;JI Hong-yan;WEI Shi-jie;FU Xue-yan;LIU Meng-ying;WU Xiu-li;School of Pharmacy,Ningxia Medical University;Institute of Clinical Pharmacology,General Hospital of Ningxia Medical University;

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