Al-Abd Ahmed M, Kim Nam Ho, Song Soo-Chang, Lee Seung Jin, Kuh Hyo-Jeong
Department of Biomedical Sciences, College of Medicine, The Catholic University of Korea, Seoul, 137-701, Korea.
Arch Pharm Res. 2009 Apr;32(4):605-11. doi: 10.1007/s12272-009-1417-5. Epub 2009 Apr 29.
Doxorubicin is a cytotoxic anthracycline that has been used for the treatment of several malignancies. Several HPLC methods have been reported for the quantification of doxorubicin in biological samples. Tissue matrix effect and sample size requirements, however, have been remaining issues for simple and easy-to-adapt analytical methods in small animal experiments. The present study established a simple HPLC method for doxorubicin in plasma and tissues (tumor, heart, spleen, liver, gastrointestinal tract, brain, lung, and kidney) of nude mice. Our method required a small sample volume (100 microL plasma and 10 mg tissue), which made it possible to use each blank tissue for calibration curves. The limit of quantification was 25 ng/mL in plasma and 0.1 to 0.4 microg/mg in other tissues with recovery rates ranging from 52.4 to 95.2%. The linearity, accuracy and precision in all tissues, except gastrointestinal tract (GIT), were found to be acceptable in the range of 25-2000 ng/mL plasma and 0.1-4 ng/mg tissue. This method was used successfully to determine the drug concentration in plasma and tissues of human tumor xenograft-bearing nude mice given intratumoral doxorubicin in a polymeric drug delivery system designed for sustained release. In conclusion, the present method may be useful as a simple and easy-to-adapt, yet, sensitive analytical method of doxorubicin for plasma and tissue pharmacokinetic studies in small animals such as nude mice.
阿霉素是一种细胞毒性蒽环类药物，已用于治疗多种恶性肿瘤。已有多种高效液相色谱（HPLC）方法用于定量生物样品中的阿霉素。然而，在小动物实验中，组织基质效应和样品量要求一直是简单且易于应用的分析方法所面临的问题。本研究建立了一种简单的HPLC方法，用于测定裸鼠血浆和组织（肿瘤、心脏、脾脏、肝脏、胃肠道、脑、肺和肾脏）中的阿霉素。我们的方法所需样品量小（100微升血浆和10毫克组织），这使得可以使用每个空白组织制作校准曲线。血浆中的定量限为25纳克/毫升，其他组织中为0.1至0.4微克/毫克，回收率在52.4%至95.2%之间。除胃肠道（GIT）外，在血浆浓度为25 - 2000纳克/毫升、组织浓度为0.1 - 4纳克/毫克的范围内，所有组织中的线性、准确度和精密度均可接受。该方法成功用于测定在一种设计用于缓释的聚合物药物递送系统中给予瘤内阿霉素的人肿瘤异种移植裸鼠血浆和组织中的药物浓度。总之，本方法可能是一种简单、易于应用且灵敏的阿霉素分析方法，可用于裸鼠等小动物的血浆和组织药代动力学研究。
