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优化 LC 方法,用于定量检测血浆和尿液样本中的阿霉素,以进行药代动力学、生物医学和药物监测治疗研究。

Optimization of LC method for the quantification of doxorubicin in plasma and urine samples in view of pharmacokinetic, biomedical and drug monitoring therapy studies.

机构信息

Department of Pharmaceutical Chemistry, Medical University of Gdańsk, Hallera 107, 80-416 Gdańsk, Poland.

Department of Pharmaceutical Chemistry, Medical University of Gdańsk, Hallera 107, 80-416 Gdańsk, Poland.

出版信息

J Pharm Biomed Anal. 2018 Sep 5;158:376-385. doi: 10.1016/j.jpba.2018.06.031. Epub 2018 Jun 19.

DOI:10.1016/j.jpba.2018.06.031
PMID:29936377
Abstract

A simple, rapid, reliable and sensitive method based on liquid chromatography with fluorescence detection (LC-FL) for the quantification of doxorubicin (DOX) in human plasma and urine samples was developed. The assay was carried out after the solid-phase extraction procedure (SPE) with hydrophilic-lipophilic balance (HLB) cartridges, and with daunorubicin hydrochloride (DAU) used as the internal standard. Chromatographic separation was performed on a Discovery HS C18 column in isocratic elution mode, and the detection of the analytes set at excitation and emission wavelengths of 487 and 555 nm, respectively. The developed LC-FL method has been validated for accuracy, precision, selectivity, linearity, recovery and stability. The limits of detection and quantification for DOX were 0.5 and 1 ng/mL in both biological fluids, respectively. Linearity was confirmed in the range of 1-1000 ng/mL and 0.001-25 μg/mL in plasma and urine samples, respectively, with a correlation coefficient greater than 0.9994. The proposed LC-FL method is selective, precise and accurate, and has been successfully applied for drug monitoring in pediatric cancer patients treated with DOX as a component of OEPA (Oncovin (Vincristine)-Etoposide-Prednisone-Adriamycin) and IOA (Ifosfamide-Oncovin-Adriamycin) chemotherapeutic schemes. Moreover, real exposure of hospital personnel to the anthracycline drugs in plasma and urine was evaluated in clinical practice.

摘要

建立了一种基于液相色谱-荧光检测(LC-FL)的简单、快速、可靠和灵敏的方法,用于定量人血浆和尿液中的多柔比星(DOX)。该测定方法采用亲水-亲脂平衡(HLB)柱固相萃取(SPE)后进行,以盐酸柔红霉素(DAU)为内标。采用 Discovery HS C18 柱在等度洗脱模式下进行色谱分离,分析物的检测波长分别为 487nm 和 555nm。所建立的 LC-FL 方法已经过准确性、精密度、选择性、线性、回收率和稳定性验证。在两种生物流体中,DOX 的检测限和定量限分别为 0.5 和 1ng/mL。在血浆和尿液样品中,线性范围分别为 1-1000ng/mL 和 0.001-25μg/mL,相关系数均大于 0.9994。该方法选择性好、精密度和准确度高,已成功应用于以 DOX 为 OEPA(长春新碱-依托泊苷-泼尼松-阿霉素)和 IOA(异环磷酰胺-长春新碱-阿霉素)化疗方案治疗的儿科癌症患者的药物监测。此外,还在临床实践中评估了医院工作人员在血浆和尿液中接触蒽环类药物的实际情况。

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