Objective

Our objective was to validate and compare the automated and chromatography methods for determining imatinib levels in plasma, in terms of linearity, precision, accuracy and specificity, for therapeutic drug monitoring.

Methods

Imatinib patterns were prepared in human plasma and were analysed by both methods to determine the calibration curve of each method. The methods were validated for linearity, extraction recovery, intra- and inter-day precision (relative standard deviation, RSD%), accuracy, and specificity of imatinib analysis. Method comparison study was carried out using the imatinib concentrations determined in the 25 patient samples by Deming regression and Bland–Altman analysis.

Results

The calibration curve of the automated and chromatography methods were linear over the range 500–2750 ng/ml (r = 0.996) and 500–3000 ng/ml (r = 0.999), respectively. Intra- and inter-day precision showed that not all the CV values of the drug were below 15% for the automated method, recommended by the EMA and the FDA. In contrast, all CV values for precision of the chromatography method are below 6.0%. Average recovery percentage is 94.4% and 100.8 for the automated and chromatography methods, respectively. Agreement between the two methods was illustrated using Bland–Altman plot with a mean difference (Immunoassay—UPLC-UV) of 191.28 ng/ml and a 95% confidence interval of − 201.41 to 583.97 ng/ml. Deming regression analysis showed that the correlation coefficient for the automated method versus the chromatography method was 0.927

Conclusions

The chromatographic technique was the better option for therapeutic drug monitoring of imatinib in clinical practice in patients with Chronic Myeloid Leukemia (CML).

中文翻译：

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伊马替尼治疗药物监测的两种分析方法的验证和比较

客观的

我们的目的是验证和比较用于线性线性，精密度，准确性和特异性的用于测定血浆伊马替尼水平的自动化和色谱方法，用于治疗药物监测。

方法

在人血浆中制备伊马替尼模式，并通过两种方法进行分析，以确定每种方法的校准曲线。验证了这些方法的线性，萃取回收率，日内和日间精度（相对标准偏差，RSD％），准确性和伊马替尼分析的特异性。方法比较研究是使用通过Deming回归和Bland–Altman分析在25个患者样品中确定的伊马替尼浓度进行的。

结果

自动和色谱方法的校准曲线在500–2750 ng / ml（r  = 0.996）和500–3000 ng / ml（r = 0.999）。日间和日间精度表明，对于自动方法，并非所有药物的CV值都低于EMA以及FDA推荐的15％。相比之下，所有色谱方法的CV值均低于6.0％。自动和色谱法的平均回收率分别为94.4％和100.8。两种方法之间的一致性使用Bland-Altman图进行了说明，平均差异（免疫测定-UPLC-UV）为191.28 ng / ml，95％置信区间为− 201.41至583.97 ng / ml。Deming回归分析显示自动化方法与色谱方法的相关系数为0.927

结论

在临床实践中，对于慢性粒细胞白血病（CML）患者，色谱技术是伊马替尼治疗药物监测的更好选择。