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无胶筛分毛细管电泳法测定猕猴血浆中的反义寡核苷酸药物癌泰得 被引量:4

Quantitative determination of Cantide,an antisense oligodeoxynucleotide in rhesus monkey plasma using non-gel sieving capillary electrophoresis method
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摘要 采用两步固相萃取(SPE)法结合无胶筛分毛细管电泳(NGCE)技术建立了猕猴血浆中的反义寡核苷酸药物癌泰得的定量分析方法。优化并确定了SPE的相关条件(阴离子交换柱,上样缓冲液pH值为9.0,上样体积及洗脱体积分别为5mL和3mL)和NGCE的分析条件(灌胶时间为30min,分离电压为24kV)。在优化的条件下,猕猴血浆中癌泰得在1.95~250mg/L范围内呈良好的线性关系,定量限(LOQ)为1.95mg/L。批内准确度为93.38%~100.71%,批内相对标准偏差<11%;批间准确度为89.46%~103.46%,批间相对标准偏差<9%。在不同条件(室温下存放4h;4℃下存放24h;反复冻融(-80℃至室温)2次;-80℃下保存1个月)下癌泰得在猕猴血浆中的稳定性良好。已将该方法成功地应用于癌泰得的猕猴药代动力学研究。 A dual solid phase extraction(SPE) pretreatment coupling with non-gel sieving capillary electrophoresis(NGCE) analysis method was established for the quantitative determination of an antisense oligodeoxynucleotide,Cantide,in rhesus monkey plasma.The conditions of SPE and the NGCE analysis were optimized.Under the optimized conditions(the SPE conditions: the pH of loading buffer was 9.0;the volumes of loading and the elution solution for the anion-exchange column were 5 mL and 3 mL,respectively.The NGCE analysis conditions: loading gel time was 30 min and the separation voltage was 24 kV),the linear dynamic range of Cantide in rhesus monkeys plasma was 1.95-250 mg/L,and the correlation coefficient(r) was more than 0.998.The limit of quantitation was 1.95 mg/L.The intra-batch accuracies ranged from 93.38% to 100.71% with the intra-batch relative standard deviation(RSD) less than 11%.The inter-batch accuracies were from 89.46% to 103.46% with the inter-batch RSD less than 9%.The stability experiment showed that the Cantide plasma sample was stable when stored at 4 ℃ for 24 h,room temperature for 4 h,-80 ℃ for 30 days and freeze-thaw for 2 cycles.This method was finally successfully applied to pharmacokinetic study of Cantide in rhesus monkeys.
出处 《色谱》 CAS CSCD 北大核心 2010年第6期561-565,共5页 Chinese Journal of Chromatography
基金 国家"863"计划项目(No.2007AA021602) 国家自然科学基金项目(No.39870879) 新药科技重大专项(No.2009ZX09503-021)
关键词 固相萃取 无胶筛分毛细管电泳 反义寡核苷酸 癌泰得 猕猴 solid phase extraction(SPE) non-gel sieving capillary electrophoresis(NGCE) antisense oligodeoxynucleotide Cantide rhesus monkey
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