目的 以肾移植患者环孢霉素A谷浓度检测结果为例, 探讨以对数正态分布为基础的换算方法在不同检测方法测定结果切换中的应用, 建立更为准确合理的测定结果转换方法。方法 将超高效液相色谱-串联质谱法(UPLC-MS/MS)和化学发光微粒子免疫分析法(CMIA)2种方法测定的环孢霉素A谷浓度数据进行对数转换, 以非参数的Kolmogorov-Smirnov检验方法确定其是否符合正态分布, 计算各方法的最佳谷浓度, 以两者比值作为方法的转换系数(CCop), 用于2种方法测定结果的快速换算, 并与传统的线性回归和均值比较方法进行对比。结果 2种方法测定结果经对数转换后符合正态分布(P>0.05), 因此符合对数正态分布特征, 转换系数CCop=1.29, 所建立的对数正态分布比较方法与线性回归方法相比在低浓度值区域权重残差(WRES)减小, 而所确定的最佳谷浓度比均值能更好地反映达到最适合药效所需调整达到的目标浓度。结论 本实验所建立的对数正态分布方法可较好的对不同检测方法的测定结果进行切换, 可在治疗药物监测中检测方法改变时对测定结果进行切换, 以便医生和临床药师进行个体化给药方案的调整。
Abstract
OBJECTIVE To discuss the application of conversion method based on lognormal distribution in comparison of different detection methods, taking cyclosporine A trough concentration in renal transplant patients for example. To establish a more accurate method for conversion of the RESULTSby different detection methods.METHODS Cyclosporine A trough concentration data measured by UPLC-MS/MS and CMIA were changed to logarithmic form, and nonparametric Kolmogorov-Smirnov test was used to analyze whether they accorded with normal distribution. The conversion coefficient (CCop) was determined by the ratio of optimal trough concentrations by the two detection methods. This conversion method was used for the rapid switch of RESULTSof the two methods, and was compared with the traditional linear regression method and average comparison method. RESULTSThe RESULTSof two METHODS accorded with normal distribution (P>0.05) after transformed logarithmically. The conversion coefficient CCopwas 1.29. Compared with linear regression method, the developed lognormal distribution method had smaller weight residues (WRES) in the low concentration region.The determined optimal c0 concentration can better reflect the target concentration for ideal pharmacological effect than the average. CONCLUSION Lognormal distribution method developed in this study can be used to switch RESULTSof the different detection METHODS better when detection METHODS change in therapeutic drug monitoring, which is available for adjustment of individualized dosing regimens.
关键词
对数正态分布 /
超高效液相色谱-串联质谱法 /
环孢霉素A /
肾移植 /
化学发光微粒子免疫分析法
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Key words
logarithmic normal distribution /
UPLC-MS/MS /
cyclosporine A /
renal transplantation /
chemiluminescent microparticle immunoassay
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中图分类号：
R927
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参考文献
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脚注
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基金
首都医学发展科研基金(2009-3021)
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