Johnson-Davis K L, Juenke J M, Thomas R L, Bradshaw T
Department of Pathology, University of Utah School of Medicine, Salt Lake City, UT ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT and
ARUP Institute for Clinical and Experimental Pathology, Salt Lake City, UT and.
Ann Clin Lab Sci. 2015 Winter;45(1):27-31.
Everolimus is an immunosuppressant drug that was approved for prophylactic use in the United States to prevent organ rejection in adult kidney and liver transplant recipients. Therapeutic drug management (TDM) is required to optimize the dose for efficacy and to minimize toxicity. Prior to the development of immunoassay reagents for everolimus, laboratory developed chromatographic methods were routinely used to support TDM for everolimus testing. However, the use of high performance liquid chromatography coupled to tandem mass spectrometry (HPLC-MS/MS)for everolimus TDM is not widely utilized in hospitals or transplant centers due to either a lack of mass spectrometry instrumentation or resources for assay development. An everolimus reagent kit and method was developed by Waters Corporation for use on the Waters ACQUITY TQD mass spectrometer system.
The purpose for this study was to evaluate the investigational use only (IUO) Waters MassTrak Immunosuppressants XE (IUO) kit on a Waters ACQUITY(®) ultra performance liquid chromatography (UPLC) coupled to an ACQUITY(®) TQD mass spectrometer and to compare this test system to a laboratory developed mass spectrometry assay for everolimus.
We evaluated precision and performed a patient comparison study on 56 renal transplant patients that received everolimus against a validated in house HPLC-MS/MS method.
5-day precision was performed on two patient pooled samples and analyzed in triplicate. Total imprecision for the low patient pool (3.77 ng/mL) and high patient pool (10.87 ng/mL) was <15 %CV. Deming regression analysis was performed for the patient comparison and the linear regression equation was y=0.973x+0.03, Sy/x 0.55, and the correlation coefficient was 0.9815.
The Waters MassTrak Immunosuppressants XE (IUO) kit and method had good correlation between the concentration range of 3-15 ng/mL to the established in-house HPLC-MS/MS method.
依维莫司是一种免疫抑制剂药物，在美国被批准用于预防性治疗，以防止成年肾移植和肝移植受者发生器官排斥反应。需要进行治疗药物监测（TDM）来优化剂量以提高疗效并将毒性降至最低。在用于依维莫司的免疫分析试剂开发之前，实验室开发的色谱方法通常用于支持依维莫司检测的TDM。然而，由于缺乏质谱仪器或分析方法开发资源，高效液相色谱-串联质谱联用（HPLC-MS/MS）用于依维莫司TDM在医院或移植中心并未得到广泛应用。沃特世公司开发了一种依维莫司试剂试剂盒和方法，用于沃特世ACQUITY TQD质谱仪系统。
本研究的目的是评估仅用于研究用途（IUO）的沃特世MassTrak免疫抑制剂XE（IUO）试剂盒在沃特世ACQUITY（®）超高效液相色谱（UPLC）与ACQUITY（®）TQD质谱仪联用系统上的性能，并将该检测系统与实验室开发的依维莫司质谱分析法进行比较。
我们评估了精密度，并对56例接受依维莫司治疗的肾移植患者进行了患者比较研究，与经过验证的内部HPLC-MS/MS方法进行对比。
在两个患者混合样本上进行了5天的精密度测试，并进行了三次重复分析。低患者混合样本（3.77 ng/mL）和高患者混合样本（10.87 ng/mL）的总不精密度<15%CV。对患者比较进行了戴明回归分析，线性回归方程为y = 0.973x + 0.03，Sy/x为0.55，相关系数为0.9815。
沃特世MassTrak免疫抑制剂XE（IUO）试剂盒和方法在3 - 15 ng/mL的浓度范围内与已建立的内部HPLC-MS/MS方法具有良好的相关性。
