关键词: 肿瘤坏死因子α;药代动力学;放射测量术;HPLC;ELISA

    摘 要:目的 为探讨新型重组人肿瘤坏死因子(nrTNFα)药代动力学而建立生物样品中nrhTNFα的检测方法. 方法 ①方法Ⅰ(RA):动物肌注125 Ⅰ标记的nrhTNFα后，测定各生物样品中的总放射活性;②方法Ⅱ(HPLC-RA):上述生物样品先经HPLC分离后，收集并测定其中125 Ⅰ-nrhTNFα部分的放射活性;③方法ⅢEILISA法. 结果 RA，HPLC-RA法检测的nrhTNFα质量浓度与放射性呈直线相关(RA，r=0.999HPLC-RA，r=0.999).ELISA法证明rhTNFα的酶联免疫检测药盒适用于nrhTNFα的检测，rhTNFα的标准曲线与nrhTNFα的标准曲线显正相关，r=0.994.这一检测系统与其他细胞因子包括IFNα，TNFβ，IL-2和IL-6无交叉反应. 结论 RA，HPLC-RA和ELISA法均可作为nrhTNFα的药代动力学实验方法.

    Pharmacokinetic methods for new recombinant hu┐man tumor necrosis factor alpha

    ZHAO Ning ZHANG Ying-Qi WANG Zeng-Lu LIU Chang-Xiao CHEN Zheng-Min GU Yi-Biao CAI Yong-Ming GAO Lian-Yong LI Quan-Sheng ZENG Yong

    1 Biotechnology Center，Fourth Military Medical U-niversity，Xi'an710033，China，

    2 Tianjin Institute of Pharmaceutical Research，Department of Nation-al Pharmaceutical Administration，Tianjin300193，China

    Keywords:tumor necrosis factor-alpha;pharrmacokinetics;radiometry;HPLC;ELISA

    Abstract:AIM To establish three methods of detecting nrh-TNFαin biological samples for investigating the pharma-cokinetics of nrhTNFα.METHODS Method I(RA):Mea-suring the total radioactivity in biological samples after125 Ⅰ-nrhTNFαadministration by im injection to animals.MethodⅡ(HPLC-RA):Collecting and measuring the radio activity of125 Ⅰ-nrhTNFαafter samples separated by HPLC.MethodⅢ:ELISA.RESULTS The mass concentrations of nrhTNFαmeasured by RA and HPLC-RA had straight line correlation with their radioactivity.It was demonstrated that the rhTNFαELISA kit was suitable for nrhTNFαdetection and both standard curves of rhTNFαand nrhTNFαhad a good positive correlation with a correlation coefficient of0.994.The ELISA system showed no cross reaction with any other cytokines including IFNα ......