伊马替尼及其代谢物血浆蛋白结合率测定方法的建立及应用
x

请在关注微信后,向客服人员索取文件

篇名: 伊马替尼及其代谢物血浆蛋白结合率测定方法的建立及应用
TITLE: Establishment and application of a method for the determination of plasma protein binding rate of imatinib and its metabolite
摘要: 目的 建立测定伊马替尼及其代谢物(N-去甲基伊马替尼)血浆蛋白结合率的方法,并应用于胃肠道间质瘤(GIST)患者。方法以伊马替尼-d8为内标,采用甲醇沉淀蛋白处理样品,以平衡透析法结合液相色谱-串联质谱法测定,并同法检测GIST患者血浆中伊马替尼及其代谢物的游离浓度。结果伊马替尼在120、4000ng/mL浓度下,与白蛋白、α1-酸性糖蛋白、球蛋白的血浆蛋白结合率分别为(92.5±1.0)%和(91.7±0.4)%、(56.6±2.0)%和(62.6±2.6)%、(56.3±3.1)%和(68.0±8.6)%;N-去甲基伊马替尼在60、2000ng/mL浓度下,上述结合率分别为(90.6±3.5)%和(91.3±1.5)%、(54.1±5.1)%和(63.7±1.3)%、(56.2±7.6)%和(67.5±7.3)%。与低浓度伊马替尼(120ng/mL)及其代谢物(60ng/mL)比较,高浓度伊马替尼(4000ng/mL)及其代谢物(2000ng/mL)与α1-酸性糖蛋白、球蛋白的血浆蛋白结合率显著提高(P<0.05),但与白蛋白的血浆蛋白结合率比较,差异无统计学意义(P>0.05)。空白血浆中,高浓度伊马替尼(4000ng/mL)及其代谢物(2000ng/mL)的血浆蛋白结合率显著低于低(120、60ng/mL)、中(750、375ng/mL)浓度(P<0.01)。GIST患者血浆中,伊马替尼及其代谢物的平均血浆蛋白结合率分别为(99.0±0.3)%、(99.2±0.3)%,伊马替尼及其代谢物的浓度与血浆蛋白结合率的相关系数分别为-0.2985、-3.3323(P均小于0.05)。结论成功建立了测定伊马替尼及其代谢物血浆蛋白结合率的方法;GIST患者伊马替尼及其代谢物的血浆蛋白结合率与药物浓度呈负相关。
ABSTRACT: OBJECTIVE To establish a method for the determination of plasma protein binding rate of imatinib and its metabolite(N-desmethyl imatinib )and apply it to patients with gastrointestinal stromal tumor (GIST).METHODS Using imatinib - d8 as the internal standard ,after being deproteinized methanol ,the sample was determined by equilibrium dialysis combined with liquid chromatography -tandem mass spectrometry . The free concentrations of imatinib and its metabolites in plasma of GIST patients were detected by the same method . RESULTS The protein binding rates of imatinib with albumin ,α1-acid glycoprotein and globulin at 120 ng/mL and 4 000 ng/mL were (92.5±1.0)% and(91.7±0.4)%,(56.6±2.0)% and(62.6±2.6)%,(56.3±3.1)% and (68.0±8.6)% ,respectively. The protein binding rates of N-desmethyl imatinib with albumin ,α1-acid glycoprotein and globulin at 60 ng/mL and 2 000 ng/mL were (90.6±3.5)% and(91.3±1.5)%,(54.1±5.1)% and(63.7±1.3)%,(56.2±7.6)% and(67.5±7.3)%,respectively. Compared with the low concentration group of imatinib (120 ng/mL)and its metabolite (60 ng/mL),the plasma protein binding rate of high concentration of imatinib (4 000 ng/mL)and its metabolite (2 000 ng/mL)with α1-acid glycoprotein and globulin was significantly increased (P< Δ基金项目 国家自然科学基金资助项目(No.81503160);江苏省 0.05),but there was no signifi -cant difference with albumin 卫生健康发展研究中心 2021年度开放课题(No.JSHD2021004);江苏 (P>0.05). In blank plasma ,the protein binding rates of imatinib(4 000 ng/mL)at high concentration and its metabolites(2 000 ng/mL)were significantly lower than those of low (120, 60 ng/mL) and medium (750, 375 ng/mL)concentration (P<0.01). Average protein binding rates of imatinib and its metabolite in plasma of GIST patients were (99.0±0.3)% and(99.2±0.3)%,respectively;the correlation coefficients between the concentrations of imatinib and its metabolites and the protein binding rates were -0.298 5 and -3.332 3,respectively(all P<0.05). CONCLUSIONS The method for determining the plasma protein binding rates of imatinib and its metabolites is successfully established . The plasma protein binding rates of imatinib and its metabolites in patients with GIST are negatively correlated with drug concentration .
期刊: 2022年第33卷第18期
作者: 王敦建,焦慧文,钱依,徐江浩,徐皓,孙鲁宁,王永庆
AUTHORS: WANG Dunjian ,JIAO Huiwen ,QIAN Yi,XU Jianghao ,XU Hao,SUN Luning ,WANG Yongqing
关键字: 伊马替尼;N-去甲基伊马替尼;平衡透析法;液相色谱-串联质谱技术;血浆蛋白结合率
KEYWORDS: imatinib;N-desmethyl imatinib ;equilibrium dialysis ;liquid chromato graphy-tandem mass spectrometry ;plasma
阅读数: 26 次
本月下载数: 2 次

* 注:未经本站明确许可,任何网站不得非法盗链资源下载连接及抄袭本站原创内容资源!在此感谢您的支持与合作!