HPLC-UV法测定人血浆及尿中多尼培南  

HPLC-UV determination of doripenem in human plasma and urine

作　　者：秦永平[1] 梅亚君 章丽[1] 毛锐[1] 南峰[1] 向瑾[1] 梁茂植[1] 余勤[1] 

机构地区：[1]四川大学华西医院临床药理研究室,四川成都610041 [2]成都中医药大学药学院,四川成都611137

出　　处：《中国测试》2015年第5期54-57,共4页China Measurement & Test

摘　　要：建立HPLC-UV法测定人血浆及尿中多尼培南(DP)的质量浓度,用于DP人体药代动力学研究。采用Ultimate XB-C18(150 mm×4.6 mm×3μm)色谱柱,血浆及尿样测定用流动相分别为10 mmol/L醋酸钠∶乙腈∶三乙胺(体积比94∶6∶0.1,冰乙酸调p H为4.51)和8 mmol/L醋酸钠∶乙腈∶三乙胺(体积比95.5∶4.5∶0.1,冰乙酸调p H值为4.99),流速均为1 m L/min,检测波长为297 nm。血浆样品经乙睛沉淀蛋白,再用二氯甲烷反洗后取上清液进样,以美罗培南(MRP)做内标;尿样直接用水稀释后进样,外标法定量。血药浓度在0.0625~200μg/m L范围内与峰面积线性关系良好,定量限为0.0625μg/m L,批内精密度在1.0%~6.0%之间,批间精密度在3.0%~6.7%之间,方法回收率在92.4%~104.5%之间,预处理回收率在91.2%~103.8%之间。尿药浓度在0.625~4 800μg/m L范围内与峰面积线性关系良好,定量限为0.625μg/m L,批内精密度在0.7%~4.0%之间,批间精密度在1.1%~5.3%之间,方法回收率在94.1%~106.7%之间。该方法具有简便、灵敏、准确等特点,适用于人血浆及尿中多尼培南质量浓度的测定。To establish a HPLC-UV method for determining Doripenem(DP) in human plasma and urine to perform DP human pharmacokinetic studies. The assay was conducted on a HPLC-UV column of Ultimate XB-C18(150mm×4.6mm×3μm). Mobile phases were 10mmol/L natrium aceticumacetonitrile-triethylamine(94∶6∶0.1(ν∶ν∶ν),p H adjusted to be 4.51 with acetic acid) and 8 mmol/L natrium aceticum-acetonitrile-triethylamine(95.5∶4.5∶0.1(ν∶ν∶ν),p H adjusted to be 4.99 with acetic acid). The above mobile phases were pumped at the rate of 1 m L/min through the column,with the detection wavelength set at 297 nm. Plasma samples were deproteinized with acetonitrile,which was extracted and removed with dichloromethane. Meropenem(MRP)was used as the internal standard(IS).Urine samples were diluted in distilled water and then quantified with the external reference method.The plasma concentration was in a linear relationship with the calibration curve within the range of0.062 5-200 μg/m L while the quantitation limit was 0.062 5 μg/m L. The within-run and between-run precisions were 1.0%-6.0% and 3.0%-6.7%,respectively. The method recovery was 92.4%-104.5%and the plasma pretreatment recovery was 91.2%-103.8%. The urine concentration had a linear correlation to the calibration curve in the range of 0.625-4 800 μg/m L while the quantization limit was 0.625 μg/m L. The within-run and between-run precision were 0.7%-4.0% and 1.1%-5.3%,respectively. The method recovery was 94.1%-106.7%. This method is simple and rapid,sensitive and accurate,suitable for determining DP concentration in human plasma and urine.

关 键 词：多尼培南 高效液相色谱法 血药浓度 尿药浓度 

分 类 号：R96[医药卫生—药理学]