高效液相色谱质谱联用检测血浆莎巴比星的基质效应影响因素

发布时间：2018-12-10 07:40

【摘要】：目的:考察EDTA-K2和肝素锂抗凝血浆不同前处理方法和液相条件对于高效液相色谱质谱联用法检测莎巴比星及其代谢产物M3基质效应的影响。方法:以含不同抗凝剂的空白血浆配制低、中、高浓度样品,乙酸乙酯或氯仿液液萃取,流动相:A:0.1%甲酸水,B:乙腈,等度洗脱或梯度洗脱。莎巴比星、M3和内标多柔比星检测离子对分别为:m/z 644→130,m/z 646→333.2,m/z 544→360。采用提取后加入法,评价各浓度莎巴比星和M3在2种抗凝剂血浆中基质效应的差异以及方法优化对基质效应的影响。结果:低浓度时,EDTA-K2组莎巴比星和M3基质效应分别为123%和110%,肝素锂组分别为143%和160%。基质效应在不同抗凝剂组间差异有统计学意义(莎巴比星:P0.05;M3:P0.05)。氯仿萃取肝素锂抗凝血浆中莎巴比星低、中、高浓度基质效应分别为142%,94%和78%,M3分别为123%,102%和89%。梯度洗脱莎巴比星低、中、高浓度基质效应分别为108%,81%和73%,而M3分别为93%,83%和73%。最终低浓度莎巴比星和M3基质效应分别为85.4%和98.7%,高浓度分别为88.5%和96.0%。结论:肝素锂抗凝血浆中莎巴比星及其代谢物M3的基质增强效应更强,且在不同浓度存在较大差异,优化前处理方法以及液相方法后基质效应得到显著改善。
[Abstract]:Aim: to investigate the effects of different pretreatment methods and liquid phase conditions of EDTA-K2 and heparin lithium anticoagulant plasma on the detection of Sababisin and its metabolite M3 matrix by HPLC / MS. Methods: low, middle and high concentration samples were prepared with blank plasma containing different anticoagulants. Ethyl acetate or chloroform was extracted by liquid solution. The mobile phase consisted of A: 0.1% formic acid water, B: acetonitrile, equal degree elution or gradient elution. The detected ion pairs of Sababisin, M3 and internal standard doxorubicin were as follows: M / z 644 ~ 130m / m / z 646 ~ 333.2m / m / z ~ (544) m / z ~ (360). The difference of matrix effect between different concentrations of Sababisin and M3 in plasma of two anticoagulants and the effect of method optimization on matrix effect were evaluated by adding method after extraction. Results: at low concentration, the matrix effects of Sababisin and M3 in EDTA-K2 group were 12.3% and 110g, and those in lithium-heparin group were 14.3% and 160g, respectively. There was significant difference in matrix effect among different anticoagulant groups (Sababisin: P0.05M3: P0.05). The medium and high concentrations of Sababisin in lithium-heparin anticoagulant plasma extracted by chloroform were 142.94% and 78-M _ 3, respectively, which were 123,102% and 89%, respectively. The matrix effect of gradient elution of Sababisin was 10881% and 73%, respectively, while M3 was 93.3% and 73.3%, respectively. The final matrix effects of Sababisin and M3 at low concentration were 85.4% and 98.7%, respectively, while those at high concentration were 88.5% and 96.0%, respectively. Conclusion: the matrix enhancement effect of Sababisin and its metabolite M3 in lithium-heparin anticoagulant plasma is stronger, and there are great differences in different concentrations.
【作者单位】：国家癌症中心/中国医学科学院北京协和医学院肿瘤医院内科抗肿瘤分子靶向药物临床研究北京市重点实验室;国家癌症中心/中国医学科学院北京协和医学院肿瘤医院检验科;
【基金】：国家“重大新药创制”科技重大专项资助项目(2012ZX09303012) 国家高技术研究发展计划(863计划)资助项目(2011AA02A110) 北京市科委重大项目(D141100000214003,D141100000214005)
【分类号】：R446.1;R969

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