采用经CE-IVD认证的液相色谱-串联质谱（LC-MS/MS）测定法对新型全自动亲和铬介导免疫测定法（ACMIA）与定量微球系统（QMS）在实体器官移植后依维莫司治疗药物监测中的互换性进行评估。

Evaluation of the interchangeability between the new fully-automated affinity chrome-mediated immunoassay (ACMIA) and the Quantitative Microsphere System (QMS) with a CE-IVD-certified LC-MS/MS assay for therapeutic drug monitoring of everolimus after solid organ transplantation.

作者信息

Ialongo Cristiano, D'alessandro Annamaria, Sapio Maria, Angeloni Antonio, Porzio Ottavia

机构信息

Department of Experimental Medicine, Policlinico Umberto I, "Sapienza" University, Rome, Italy.

Clinical Biochemistry Laboratory, IRCCS "Bambino Gesù" Children's Hospital, Rome, Italy.

出版信息

Clin Chem Lab Med. 2022 Nov 4;61(2):245-250. doi: 10.1515/cclm-2022-0699. Print 2023 Jan 27.

DOI:10.1515/cclm-2022-0699

PMID:36330751

Abstract

OBJECTIVES

This study aims to evaluate the interchangeability between the Siemens Healthineers' "EVRO" new affinity chrome-mediated immunoassay (ACMIA/EVRO) and Thermo Fisher Scientific's "EVER" Quantitative Microsphere System (QMS/EVER) with Chromsystems' CE-IVD-certified "MassTox" liquid-chromatography/tandem-mass spectrometry (LC-MS/MS) assay for the therapeutic drug monitoring of everolimus.

METHODS

A single lot of reagent, calibrators and controls were used for each assay. A total of 67 whole blood samples (n=67) from patients receiving solid organ transplant were analyzed (n=31 with kidney transplant and n=36 with liver transplant); Passing-Bablok regression and Bland-Altman difference plot were used to evaluate bias and individual agreement; LC-MS/MS analysis was used to measure the actual concentrations of calibrators and controls compared to the assigned value.

RESULTS

ACMIA/EVRO did not show any systematic bias compared to LC-MS/MS (intercept=0.244 ng/mL, 95% CI: -0.254 to 0.651 ng/mL). Nevertheless, significant proportional bias (slope=1.511, 95% CI: 1.420 to 1.619) associated to a combined bias of 44.8% (95% CI: 41.2-48.3%) was observed. Conversely, QMS/EVER did not show any bias at both systematic (intercept=-0.151 ng/mL, 95% CI: -0.671 to 0.256 ng/mL) and proportional level (slope=0.971, 95% CI: 0.895 to 1.074) with a non-statistically significant combined bias of -3.6% (95% CI: -8.4-1.1%). Based on a concentration of calibrators and controls above the assigned value for both the analytical methods, in the ACMIA/EVRO a correction which was approximately one-third of the correction for the QMS/EVER was observed.

CONCLUSIONS

ACMIA/EVRO but not QMS/EVER shows a lack of interchangeability with the CE-IVD-certified LC-MS/MS assay. We hypothesize that, as the ACMIA/EVRO uses an anti-sirolimus antibody, the under-corrected assigned value in the assay calibrators was not sufficient to reproduce the everolimus metabolites cross-reactivity occurring in real samples.

摘要

目的

本研究旨在评估西门子医疗公司的“EVRO”新型亲和铬介导免疫分析（ACMIA/EVRO）与赛默飞世尔科技公司的“EVER”定量微球系统（QMS/EVER），以及Chromsystems公司经CE-IVD认证的“MassTox”液相色谱/串联质谱（LC-MS/MS）分析法在监测依维莫司治疗药物时的互换性。

方法

每种分析方法使用同一批次的试剂、校准品和质控品。对67例接受实体器官移植患者的全血样本（n = 67）进行分析（肾移植患者31例，肝移植患者36例）；采用Passing-Bablok回归分析和Bland-Altman差异图评估偏差和个体一致性；通过LC-MS/MS分析测量校准品和质控品相对于指定值的实际浓度。

结果

与LC-MS/MS相比，ACMIA/EVRO未显示任何系统偏差（截距 = 0.244 ng/mL，95%置信区间：-0.254至0.651 ng/mL）。然而，观察到显著的比例偏差（斜率 = 1.511，95%置信区间：1.420至1.619），合并偏差为44.8%（95%置信区间：41.2 - 48.3%）。相反，QMS/EVER在系统偏差（截距 = -0.151 ng/mL，95%置信区间：-0.671至0.256 ng/mL）和比例偏差水平（斜率 = 0.971，95%置信区间：0.895至1.074）均未显示任何偏差，合并偏差为-3.6%，差异无统计学意义（95%置信区间：-8.4 - 1.1%）。基于两种分析方法校准品和质控品浓度均高于指定值，在ACMIA/EVRO中观察到的校正约为QMS/EVER校正的三分之一。