University of Pittsburgh, Presbyterian Hospital–Shadyside, Pittsburgh, PA, USA.
Am J Clin Pathol. 2013 Jun;139(6):788-92. doi: 10.1309/AJCPB6EUC5QHLGNV.
FK506 (tacrolimus), a macrolide immunosuppressant, is widely used in pediatric transplant patients, but a relatively narrow therapeutic window in children vs adults requires close and accurate monitoring of whole blood FK506 levels. High-pressure liquid chromatography/tandem mass spectrometry (HPLC/MS/MS)-based assays have been viewed as the gold standard but are more time and labor intensive than cloned enzyme donor immunoassay (CEDIA). To analyze differences between the 2 assays, we assayed FK506 in 348 split samples simultaneously by both methods. A further 70 samples were stratified by organ transplantation type: cardiac (13%), renal (23%), small bowel (22%), or liver transplantation (42%). Results were analyzed using standard statistical techniques for method comparison. CEDIA overestimated the FK506 value relative to HPLC/MS/MS by more than 20% in 40% of cases (139/348), whereas CEDIA underestimated the FK506 value relative to HPLC/MS/MS by more than 20% in 13.5% of cases, for a total inaccuracy of 53% using a ±20% cutoff. Only 28% of samples (99/348) measured by CEDIA were within 10% of the value obtained by HPLC/MS/MS. Bland-Altman analysis showed a mean bias of 9.5% in favor of CEDIA over HPLC/MS/MS (95% confidence interval, 6.1%-12.9%). Positive bias was greatest for liver transplant and R(2) values were lowest for intestinal transplant patients, indicating that HPLC/MS/MS may be a better option for this pediatric transplant subgroup.
FK506（他克莫司），一种大环内酯类免疫抑制剂，广泛用于儿科移植患者，但与成人相比，儿童的治疗窗较窄，需要密切准确地监测全血 FK506 水平。基于高效液相色谱/串联质谱（HPLC/MS/MS）的检测方法被视为金标准，但比克隆酶供体免疫分析（CEDIA）更耗时费力。为了分析两种检测方法之间的差异，我们同时用两种方法对 348 个分割样本进行了 FK506 检测。进一步对 70 个样本按器官移植类型分层：心脏（13%）、肾脏（23%）、小肠（22%）或肝脏移植（42%）。使用标准统计方法对方法比较进行了结果分析。在 40%的情况下（139/348），CEDIA 相对于 HPLC/MS/MS 高估了 FK506 的值超过 20%，而在 13.5%的情况下，CEDIA 相对于 HPLC/MS/MS 低估了 FK506 的值超过 20%，总误差率为 53%，采用 ±20%的截定点。用 CEDIA 测量的样本中只有 28%（99/348）在 HPLC/MS/MS 获得值的 10%以内。Bland-Altman 分析显示，CEDIA 相对于 HPLC/MS/MS 的平均偏差为 9.5%（95%置信区间，6.1%-12.9%），偏向于 CEDIA。对于肝脏移植，正偏差最大，对于肠道移植患者，R²值最低，这表明 HPLC/MS/MS 可能是该儿科移植亚组的更好选择。
