Department of Clinical Pharmacology, University Hospital of Montpellier, Montpellier, France.
Department of Biochemistry, Centre Ressources Biologiques de Montpellier, University Hospital of Montpellier, Montpellier, France.
J Oncol Pharm Pract. 2022 Jan;28(1):55-63. doi: 10.1177/1078155220983407. Epub 2021 Jan 11.
Methotrexate requires therapeutic drug monitoring in oncology because of narrow therapeutic index, especially the metabolite 7-hydroxymethotrexate exhibits nephrotoxicity. The goal of this study was to evaluate different assays and their impact on clinical decisions.
Following routine measurement with Abbott TDxFLx® assay (MTX-TDX), 62 samples were analysed on Architect®i1000 (MTX-ARCHI), Xpand® (ARK/XPND), Indiko® (ARK/INDI), and HPLC (MTX-HPLC) as the reference method. The influence of 7-hydroxymethotrexate was explored on ARK reagent to document the cause of the observed bias. ROC curves were built to study the impact of the method on the discharge thresholds for the patients at three levels.
Total imprecision was below 2.60% for the methotrexate-ARCHI and close to 10% for both ARK assays for plasma pools. The correlation coefficients were 0.93, 0.93, 0.89 and 0.95, the Bland-Altman difference plot revealed a bias of 0.075, 0.037, 0.049 and -0.002, and the number of results exceeding the TE criteria of 0.1 µM was 17 (27%), 13 (21%), 15 (24%) and 15 (24%) for MTX-TDX, ARK/INDI, ARK/XPND and MTX-ARCHI, respectively. Cross reactivity with 7-hydroxymethotrexate was between 1 and 9%. Overestimation of methotrexate concentration was between -4% and +32%. The most robust clinical level was found to be the highest level (0.2 µM) with ROC curves.
The authors found the best results for imprecision with chemiluminescent microparticle immunoassay method on methotrexate-ARCHI, with bias below to the RICOS recommendations and best correlation to the reference method. Impact on the threshold values for clinical decision need to be clearly exposed to clinicians.
甲氨蝶呤由于治疗指数较窄，特别是代谢产物 7-羟甲氨蝶呤具有肾毒性，因此在肿瘤学中需要进行治疗药物监测。本研究的目的是评估不同的检测方法及其对临床决策的影响。
在常规使用雅培 TDxFLx®检测法（MTX-TDX）后，对 62 个样本分别用 Architect®i1000（MTX-ARCHI）、Xpand®（ARK/XPND）、Indiko®（ARK/INDI）和高效液相色谱法（MTX-HPLC）进行分析，以 HPLC 作为参考方法。研究 7-羟甲氨蝶呤对 ARK 试剂的影响，以确定观察到的偏差原因。绘制 ROC 曲线，以研究方法对三个水平患者出院阈值的影响。
MTX-ARCHI 的总不精密度低于 2.60%，而 ARK 两种检测方法的总不精密度均接近 10%。血浆池的相关系数分别为 0.93、0.93、0.89 和 0.95，Bland-Altman 差值图显示偏差为 0.075、0.037、0.049 和-0.002，超过 0.1µM TE 标准的结果数量分别为 17（27%）、13（21%）、15（24%）和 15（24%），对应 MTX-TDX、ARK/INDI、ARK/XPND 和 MTX-ARCHI。与 7-羟甲氨蝶呤的交叉反应性在 1 到 9%之间。甲氨蝶呤浓度的高估范围在-4%到+32%之间。研究发现，ROC 曲线显示，最稳健的临床水平是最高水平（0.2µM）。
作者发现基于化学发光微粒子免疫分析法的 MTX-ARCHI 检测方法在检测甲氨蝶呤时具有最佳的精密度，偏差低于 RICOS 建议值，与参考方法的相关性最佳。需要向临床医生明确说明对临床决策阈值的影响。
