Rogosin Institute, New York, NY, USA.
Clin Chem. 2011 Dec;57(12):1739-47. doi: 10.1373/clinchem.2011.172080. Epub 2011 Oct 13.
Owing to the lack of an internationally recognized tacrolimus reference material and reference method, current LC-MS and immunoassay test methods used to monitor tacrolimus concentrations in whole blood are not standardized. The aim of this study was to assess the need for tacrolimus assay standardization.
We sent a blinded 40-member whole-blood tacrolimus proficiency panel (0-30 μg/L) to 22 clinical laboratories in 14 countries to be tested by the following assays: Abbott ARCHITECT (n = 17), LC-MS (n = 9), and Siemens Dade Dimension (n = 5). Selected LC-MS laboratories (n = 4) also received a common calibrator set. We compared test results to a validated LC-MS method. Four samples from the proficiency panel were assigned reference values by using exact-matching isotope-dilution mass spectrometr at LGC.
The range of CVs observed with the tacrolimus proficiency panel was as follows: LC-MS 11.4%-18.7%, ARCHITECT 3.9%-9.5%, and Siemens Dade 5.0%-48.1%. The range of historical within-site QC CVs obtained with the use of 3 control concentrations were as follows: LC-MS low 3.8%-10.7%, medium 2.0%-9.3%, high 2.3%-9.0%; ARCHITECT low 2.5%-9.5%, medium 2.5%-8.6%, high 2.9%-18.6%; and Siemens/Dade Dimension low 8.7%-23.0%, medium 7.6%-13.2%, high 4.4%-10.4%. Assay bias observed between the 4 LC-MS sites was not corrected by implementation of a common calibrator set.
Tacrolimus assay standardization will be necessary to compare patient results between clinical laboratories. Improved assay accuracy is required to provide optimized drug dosing and consistent care across transplant centers globally.
由于缺乏国际认可的他克莫司参考物质和参考方法，目前用于监测全血中他克莫司浓度的 LC-MS 和免疫测定检测方法尚未标准化。本研究旨在评估他克莫司检测标准化的必要性。
我们向 14 个国家的 22 个临床实验室发送了一个盲法的全血他克莫司能力验证小组（0-30μg/L），由以下检测方法进行检测：雅培 ARCHITECT（n=17）、LC-MS（n=9）和西门子 Dade Dimension（n=5）。选定的 LC-MS 实验室（n=4）也收到了一套共同的校准器。我们将测试结果与经过验证的 LC-MS 方法进行了比较。通过 LGC 的精确匹配同位素稀释质谱法，对能力验证小组的四个样本分配了参考值。
使用他克莫司能力验证小组观察到的 CV 范围如下：LC-MS 为 11.4%-18.7%、ARCHITECT 为 3.9%-9.5%和西门子 Dade 为 5.0%-48.1%。使用 3 个对照浓度获得的历史内部 QC CV 范围如下：LC-MS 低值为 3.8%-10.7%、中值为 2.0%-9.3%、高值为 2.3%-9.0%；ARCHITECT 低值为 2.5%-9.5%、中值为 2.5%-8.6%、高值为 2.9%-18.6%；和西门子/戴德 Dimension 低值为 8.7%-23.0%、中值为 7.6%-13.2%、高值为 4.4%-10.4%。四个 LC-MS 地点之间观察到的检测偏倚未通过实施共同校准器集得到纠正。
为了在临床实验室之间比较患者结果，有必要对他克莫司检测进行标准化。需要提高检测准确性，以在全球移植中心提供优化的药物剂量和一致的护理。
