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衍生化高效液相色谱法测定血浆中顺氯氨铂的浓度

DERIVATIVE HPLC DETERMINATION OF CISPLATIN IN PLASMA

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【作者】 冯宁平; 卢素琳; 陆明廉; 谢瑞祥;

【Author】 Feng Ningping, Lu Shuling, Ln Minglian, Xie Kuixiang (Department of Analytical Chemistry, School of Pharmacy,Shanghai Medical University, Shanghai)

【机构】 上海医科大学药学院分析化学教研室; 贵州贵阳医学院药学系药理教研室; 上海医科大学药学院分析化学教研室 1986届药学专业毕业生;

【摘要】 本工作研究和改进了衍生化高效液相色谱法(HPLC)测定血浆中顺氯氨铂浓度的方法。顺氯氨铂在柱前用二乙基二硫代氨基甲酸钠衍生化,其产物在254nm波长处检出。流动相为甲醇:水(4:1,V/v),流速为1.0ml/min。固定相为YWG-G18H37(5μm)化学键合固定相,以NiCl2为内标物,顺氯氨铂与内标的保留时间分别为5.41和7.16min,本法最低检测浓度为10.8ng/ml血浆,CV%<7.5%。操作简便,适合于顺氯氨铂在体内药物动力学研究和临床血药浓度监测。

【Abstract】 A modified derivative HPLC method using for quantitative determination of cisplatin in plasma was studied and established. Oisplatin reacted directly in plasma with sodium diethyldithiooarbamate producing the Pt (DDTC)2 complex which was extracted by ethyl ether, and could be detected at 254nm. Ohromato--graphy was carried out on a y YWG-C18H37 column using methanol: water (80:20, V/ V) mobile phase at a flow rate of 1.0ml/min. Nickel Chloride was used as an internal standard. The minimal detectable concentration of this method was 10.8ng/ml. The correlation ratio of the cisplatin and that of the internal standard against cisplatin concentrations was linear with a correlation coefficient of 0.999 2 over a range oi 0.064 8 bo 0.64 8μg/ml. The recovery were 100.1%+0.643 at drug levels of 0.162, 0.486 and 0.810μg/ml. The C. V.% was less than 7.5%. Recovery of this ethyl ether extraction is 96.65%+1.145. This is much higher than when OHCl3 was used as the extractive solvent.The pharmacokinetio characteristics of oisplatin were studied in five rabbits after intravenous administration (2.0mg/kg). The pharmaookinetio parameters were calculated by the PK computer program. The method described here is adequate for clinical drug monitoring and pharmacokinetio studies in human beings.

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