Pharmacokinetics and Therapeutic Drug Monitoring Unit, Department of Pharmacology and Clinical Investigation Center (CIC-1901), AP-HP, Sorbonne Université, Paris, France.
Department of Pathology, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
Clin Chem Lab Med. 2022 Sep 2;60(11):1753-1762. doi: 10.1515/cclm-2021-1340. Print 2022 Oct 26.
All guidelines recommend LC-MS/MS as the analytical method of choice for the quantification of immunosuppressants in whole blood. Until now, the lack of harmonization of methods and the complexity of the analytical technique have prevented its widespread use in clinical laboratories. This can be seen in international proficiency schemes, where more than half of the participants used immunoassays. With the Cascadion SM Clinical analyzer (Thermo Fisher Scientific, Oy, Vantaa, FI) a fully automated LC-MS/MS system has been introduced, which enables the use of LC-MS/MS without being an expert in mass spectrometry.
To verify the interlaboratory comparison of the immunosuppressant assay on this type of instrument, three centers across Europe compared 1097 routine whole blood samples, each site sharing its own samples with the other two. In other experiments, the effects of freezing and thawing of whole blood samples was studied, and the use of secondary cups instead of primary tubes was assessed.
In the Bland-Altman plot, the comparison of the results of tacrolimus in fresh and frozen samples had an average bias of only 0.36%. The respective data for the comparison between the primary and secondary tubes had an average bias of 1.14%. The correlation coefficients for patient samples with cyclosporine A (n=411), everolimus (n=139), sirolimus (n=114) and tacrolimus (n=433) were 0.993, 0.993, 0.993 and 0.990, respectively.
The outcome of this study demonstrates a new level of result harmonization for LC-MS/MS based immunosuppressant analysis with a commercially available fully automated platform for routine clinical application.
所有指南均推荐 LC-MS/MS 作为全血中免疫抑制剂定量的首选分析方法。到目前为止，方法缺乏一致性和分析技术的复杂性阻碍了其在临床实验室中的广泛应用。这一点在国际能力验证计划中可见一斑，其中超过一半的参与者使用免疫测定法。Thermo Fisher Scientific Oy（芬兰万塔）的 Cascadion SM 临床分析仪引入了一种全自动 LC-MS/MS 系统，即使您不是质谱专家，也可以使用 LC-MS/MS。
为了验证该仪器上免疫抑制剂检测的实验室间比较，欧洲的三个中心比较了 1097 份常规全血样本，每个中心与另外两个中心共享自己的样本。在其他实验中，研究了全血样本冷冻和解冻的影响，并评估了使用副管而不是原管的情况。
在 Bland-Altman 图中，新鲜和冷冻样本中环孢素 A 结果的比较平均偏差仅为 0.36%。原管和副管之间比较的相应数据平均偏差为 1.14%。环孢素 A（n=411）、依维莫司（n=139）、西罗莫司（n=114）和他克莫司（n=433）患者样本的相关系数分别为 0.993、0.993、0.993 和 0.990。
本研究的结果表明，对于基于 LC-MS/MS 的免疫抑制剂分析，使用市售的全自动平台进行常规临床应用，结果的一致性达到了一个新的水平。
