ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT 84108-1221, USA.
Ther Drug Monit. 2011 Jun;33(3):315-20. doi: 10.1097/FTD.0b013e318214cd75.
Busulfan is a chemotherapeutic agent commonly used for myeloablative conditioning regimens such as in the treatment of chronic myelogenous leukemia. Busulfan dosing is complex due to wide interpatient variability in pharmacokinetics and a narrow therapeutic range. Although busulfan dose is normalized to body weight, therapeutic drug monitoring (TDM) using area under the plasma concentration curve is recommended after the first dose. A high busulfan area under the plasma concentration curve (>1500 μM·min) is associated with an increased risk for sinusoidal obstruction syndrome, and a suboptimal area under the plasma concentration curve (<900 μM·min) is associated with an increased risk for graft rejection or disease relapse. TDM of busulfan is not widely available due to the lack of commercially available and rapid methods to determine the area under the plasma concentration curve.
The purpose of this study was to evaluate the Roche cobas c 111 instrument, a photometric automated chemistry analyzer, using the Busulfan PCM assay from Saladax Biomedical Inc. The assay using this instrument was compared with an enzyme-linked immunosorbent assay (ELISA) from Saladax Biomedical Inc and the Olympus AU400e. Linearity and accuracy were evaluated between 175 and 1750 ng/mL. Imprecision was determined by analyzing 5 concentrations of standards twice a day for 20 days.
Linearity for the Roche method had a slope and y-intercept of 1.050 and -5.5, respectively, and percent recovery ranged between 95% and 105%. Correlation between the Roche and ELISA platforms was analyzed by linear regression on 26 frozen patient samples. The results from the comparison of the methods based on the Roche and ELISA platforms were as follows: coefficient of determination (R2) was 0.9684, with a slope and y-intercept of 0.752 and 108.41, respectively. Correlation between the Roche and Olympus instruments was analyzed by linear regression and Bland-Altman plots. The coefficient of determination (R2) was 0.9942, with a slope and y-intercept of 1.035 and -41.3326, respectively.
Availability of TDM of busulfan can be improved by the use of commercially available reagents and automated platforms.
白消安是一种常用于骨髓清除性预处理方案的化疗药物，例如治疗慢性髓性白血病。由于药代动力学的个体间差异很大，治疗范围较窄，因此白消安的剂量很复杂。尽管白消安剂量根据体重进行了标准化，但建议在首次给药后使用血浆浓度曲线下面积进行治疗药物监测（TDM）。较高的白消安血浆浓度曲线下面积（>1500μM·min）与窦状隙阻塞综合征的风险增加有关，而较低的白消安血浆浓度曲线下面积（<900μM·min）与移植物排斥或疾病复发的风险增加有关。由于缺乏商业上可获得的快速方法来确定血浆浓度曲线下面积，因此白消安的 TDM 并不广泛。
本研究旨在评估罗氏 cobas c 111 仪器，一种光度自动化学分析仪，使用沙拉达克斯生物医学公司的白消安 PCM 检测法。该检测法使用该仪器与沙拉达克斯生物医学公司的酶联免疫吸附测定法（ELISA）和奥林巴斯 AU400e 进行比较。在 175 至 1750ng/mL 之间评估线性和准确性。通过每天分析 5 个浓度的标准品两次，连续 20 天来确定精密度。
罗氏方法的线性斜率和 y 截距分别为 1.050 和-5.5，回收率在 95%至 105%之间。对 26 个冷冻患者样本进行线性回归分析，比较罗氏和 ELISA 平台之间的相关性。基于罗氏和 ELISA 平台的方法比较结果如下：决定系数（R2）为 0.9684，斜率和 y 截距分别为 0.752 和 108.41。通过线性回归和 Bland-Altman 图分析罗氏和奥林巴斯仪器之间的相关性。决定系数（R2）为 0.9942，斜率和 y 截距分别为 1.035 和-41.3326。
通过使用商业上可获得的试剂和自动化平台，白消安 TDM 的可用性可以得到提高。
