Hoffer Erica, Kurnik Daniel, Efrati Edna, Scherb Inna, Karasik Marina, Ring Gil, Bentur Yedidia
*Laboratory of Toxicology, Pharmacology and Pharmacogenetics; †Israel Poison Information Center; and ‡Clinical Pharmacology Unit, Rambam Health Care Campus, The Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
Ther Drug Monit. 2015 Apr;37(2):214-9. doi: 10.1097/FTD.0000000000000126.
Liquid chromatography with mass spectrometry (LC-MS/MS) is the method of choice for the determination of everolimus whole blood concentrations but is not always available. Therefore, immunoassays have been developed for clinical monitoring of everolimus. In previous studies, the Quantitative Microsphere System (QMS) immunoassay had a positive bias compared with LC-MS/MS, but was judged acceptable, although clinical agreement (eg, 95% limits of agreement) was not reported. The objective of this study was to assess whether the agreement between the QMS assay and an LC-MS/MS method was clinically acceptable for use interchangeably in therapeutic everolimus monitoring.
Whole blood samples from organ-transplanted patients on everolimus therapy were analyzed by both QMS (on Architect ci4100 analyzer) and LC-MS/MS. Paired results were compared using paired Student t test, Bland-Altman plots, and Deming regression analysis. The proportions of falsely supratherapeutic and subtherapeutic results on the QMS assay compared with the LC-MS/MS were calculated.
Among 250 samples (169 patients), mean everolimus concentrations determined by LC-MS/MS and QMS assays were 4.8 ± 2.1 ng/mL and 6.3 ± 2.1 ng/mL, respectively (P < 0.001), with 95% lines of agreement between -2.1 and 5.2 ng/mL, a range corresponding to 152% of the mean concentration. When stratified by the type of transplant, a similar positive bias was found in each subgroup (all P < 0.014). Sixty-nine percent of the samples yielding supratherapeutic concentrations (>8 ng/mL) on the QMS assay were within the therapeutic range on the LC-MS/MS.
The everolimus QMS immunoassay, using the Architect ci4100 analyzer, had a significant positive bias compared with LC-MS/MS, with a wide range between the limits of agreement. The lack of agreement may result in inadequate everolimus dose adjustments, suggesting that the QMS assay cannot be used interchangeably with the LC-MS/MS method for therapeutic everolimus monitoring in organ-transplanted patients.
液相色谱 - 质谱联用（LC-MS/MS）是测定依维莫司全血浓度的首选方法，但并非总是可用。因此，已开发出免疫测定法用于依维莫司的临床监测。在先前的研究中，定量微球系统（QMS）免疫测定法与LC-MS/MS相比存在正偏差，但尽管未报告临床一致性（例如，95%一致性界限），仍被判定为可接受。本研究的目的是评估QMS测定法与LC-MS/MS方法之间的一致性在依维莫司治疗监测中是否可临床接受以相互替代使用。
对接受依维莫司治疗的器官移植患者的全血样本，采用QMS（在Architect ci4100分析仪上）和LC-MS/MS进行分析。使用配对学生t检验、Bland-Altman图和Deming回归分析比较配对结果。计算QMS测定法与LC-MS/MS相比出现假超治疗和亚治疗结果的比例。
在250份样本（169例患者）中，LC-MS/MS和QMS测定法测定的依维莫司平均浓度分别为4.8±2.1 ng/mL和6.3±2.1 ng/mL（P<0.001），95%一致性界限在-2.1至5.2 ng/mL之间，该范围相当于平均浓度的152%。按移植类型分层时，每个亚组均发现类似的正偏差（所有P<0.014）。QMS测定法得出超治疗浓度（>8 ng/mL）的样本中，69%在LC-MS/MS测定中处于治疗范围内。
使用Architect ci4100分析仪的依维莫司QMS免疫测定法与LC-MS/MS相比存在显著正偏差，一致性界限之间范围较宽。缺乏一致性可能导致依维莫司剂量调整不足，这表明在器官移植患者的依维莫司治疗监测中，QMS测定法不能与LC-MS/MS方法相互替代使用。
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