DETERMINATION OF IMIPENEM (N-FORMIMIDOYL THIENAMYCIN) IN HUMAN-PLASMA AND URINE BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY, COMPARISON WITH MICROBIOLOGICAL METHODOLOGY AND STABILITY
DETERMINATION OF IMIPENEM (N-FORMIMIDOYL THIENAMYCIN) IN HUMAN-PLASMA AND URINE BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY, COMPARISON WITH MICROBIOLOGICAL METHODOLOGY AND STABILITY
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DOI：
10.1016/0378-4347(84)80069-9
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发表时间：
1984-01-01
期刊：
影响因子：
--
通讯作者：
BAYNE, WF
中科院分区：
文献类型：
--
作者：
GRAVALLESE, DA;MUSSON, DG;BAYNE, WF
本文建立了高效液相色谱法（HPLC）测定人血浆和尿液中抗生素亚胺培南（N-甲酰亚胺硫霉素）的含量。血浆测定方法中使用反相分析柱，尿液测定方法中使用阳离子交换柱。两种方法均在移动的相中使用硼酸盐缓冲液。针对亚胺培南在水性缓冲液、吗啉缓冲液-乙二醇稳定剂以及尿液和血浆中的稳定性，对HPLC注射用人体液样品的制备方法进行了优化。进样至HPLC系统前的样品制备包括血浆/尿液样品的脱蛋白/过滤。开放的内酰胺代谢物和共同给予脱氢肽酶抑制剂，西司他丁钠，不干扰313-nm检测亚胺培南在血浆或尿液分析。泰纳霉素是亚胺培南的前体，也是亚胺培南制剂中的一种杂质，使用这两种方法可以将泰纳霉素与药物分离。对2名健康志愿者的血浆和尿液样本进行HPLC分析所得的浓度与使用微生物测定方法的结果相比具有优势。2种方法的相关性给出r. 0.990两种液体。
High-performance liquid chromatographic (HPLC) methods using UV detection have been developed for the assay of the antibiotic imipenem (N-formimidoyl thienamycin) in human plasma and urine. A reversed-phase analytical column is employed in the plasma assay method and a cation-exchange column is used in the urine assay method. Both methods use borate buffer in the mobile phase. The method of preparation of human fluid samples for HPLC injection has been optimized with respect to the stability of imipenem in aqueous buffers, in morpholine buffer-ethylene glycol stabilizer and in urine and plasma. Preparation of the samples before injection into the HPLC systems involves deproteination/filtration of the plasma/urine samples. The open lactam metabolite and the coadministered dehydropeptidase inhibitor, cilastatin sodium, did not interfere with the 313-nm detection of imipenem in either the plasma or the urine assay. Thienamycin, the precursor of imipenem and an impurity in imipenem formulations, is separted from the drug using both of these methods. Concentrations generated from the HPLC analysis of plasma and urine samples from 2 healthy volunteers compared favorably with results using a microbiological assay method. Correlation of the 2 methods gives r .gtoreq. 0.990 for both fluids.