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[采用柱切换的高效液相色谱法测定体液中新型喹诺酮类药物及其在药物相互作用中的应用]

[Development of measurement of new quinolones in body fluids by HPLC using column switching and their application to drug interaction].

作者信息

Kudo M, Ohkubo T, Sugawara K

机构信息

Department of Pharmacy, Hirosaki University Hospital, 53 Honcho, Hirosaki 036-8563, Japan.

出版信息

Yakugaku Zasshi. 2001 May;121(5):319-26. doi: 10.1248/yakushi.121.319.

DOI:10.1248/yakushi.121.319
PMID:11360486
Abstract

A high-performance liquid chromatography (HPLC) assay was developed for the determination of 6 new quinolones in the plasma. The plasma samples were directly introduced onto a HPLC column after filtering through a Molcut II membrane filter, which removes high molecular weight proteins. New quinolone in filtrate was separated from interfering substances and retained on a pre-column using an ODS stationary phase and then was introduced onto an analytical column with an ODS stationary phase by column switching. New quinolones were detected by ultraviolet absorbance in the range of 269-300 nm. Determinations of new quinolones were possible over the concentration range of 50-4000 ng/ml; the limits of detection were 20 ng/ml. The recoveries of the new quinolones added to the plasma were 96.1-101.4% with a coefficient of variation of less than 5.0%. These methods were applied to drug level monitoring in the plasma of patients treated with new quinolones and in that of healthy volunteers participating in pharmacokinetic studies. In addition, these methods were applied to a drug interaction between new quinolones and metal cation (e.g.; Mg2+, Al3+ or Fe2+) containing agents. Furthermore, this method was applied to the determination of skin tissue level of ofloxacin in patients after treatment with ofloxacin. A correlation between serum levels and skin tissue levels of ofloxacin was determined for 30 patients after oral administration of ofloxacin. A good correlation was obtained and the coefficient of the correlation was 0.84.

摘要

建立了一种高效液相色谱(HPLC)法,用于测定血浆中的6种新型喹诺酮类药物。血浆样品经Molcut II膜滤器过滤后直接进样到HPLC柱上,该滤器可去除高分子量蛋白质。滤液中的新型喹诺酮类药物与干扰物质分离,并使用ODS固定相保留在预柱上,然后通过柱切换进样到具有ODS固定相的分析柱上。通过在269 - 300 nm范围内的紫外吸光度检测新型喹诺酮类药物。新型喹诺酮类药物在50 - 4000 ng/ml的浓度范围内均可测定;检测限为20 ng/ml。添加到血浆中的新型喹诺酮类药物的回收率为96.1 - 101.4%,变异系数小于5.0%。这些方法应用于接受新型喹诺酮类药物治疗的患者血浆以及参与药代动力学研究的健康志愿者血浆中的药物浓度监测。此外,这些方法还应用于新型喹诺酮类药物与含金属阳离子(如Mg2+、Al3+或Fe2+)的药物之间的药物相互作用研究。此外,该方法还应用于氧氟沙星治疗后患者皮肤组织中氧氟沙星水平的测定。对30例口服氧氟沙星后的患者,测定了血清水平与皮肤组织中氧氟沙星水平之间的相关性。获得了良好的相关性,相关系数为0.84。

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