Morris Raymond G, Salm Paul, Taylor Paul J, Wicks Fiona A, Theodossi Anastasia
Department of Cardiology and Clinical Pharmacology, The Queen Elizabeth Hospital, Woodville, Australia.
Ther Drug Monit. 2006 Apr;28(2):164-8. doi: 10.1097/01.ftd.0000199360.25755.20.
Therapeutic monitoring with dosage individualization of sirolimus drug therapy is standard clinical practice for organ transplant recipients. For several years sirolimus monitoring has been restricted as a result of lack of an immunoassay. The recent reintroduction of the microparticle enzyme immunoassay (MEIA) for sirolimus on the IMx analyser has the potential to address this situation. This study, using patient samples, has compared the MEIA sirolimus method with an established HPLC-tandem mass spectrometry method (HPLC-MS/MS). An established HPLC-UV assay was used for independent cross-validation. For quality control materials (5, 11, 22 microg/L), the MEIA showed acceptable validation criteria based on intra- and inter-run precision (CV) and accuracy (bias) of <8% and <13%, respectively. The lower limit of quantitation was found to be approximately 3 microg/L. The performance of the immunoassay was compared with HPLC-MS/MS using EDTA whole-blood samples obtained from various types of organ transplant recipients (n = 116). The resultant Deming regression line was: MEIA =1.3 x HPLC-MS/MS + 1.3 (r = 0.967, S(y/x) = 1) with a mean bias of 49.2% +/- 23.1% (range, -2.4% to 128%; P<0.001). The reason for the large and variable bias was not explored in this study, but the sirolimus-metabolite cross-reactivity with the MEIA antibody could be a substantive contributing factor. Whereas the MEIA sirolimus method may be an adjunct to sirolimus dosage individualization in transplant recipients, users must consider the implications of the substantial and variable bias when interpreting results. In selected patients where difficult clinical issues arise, reference to a specific chromatographic method may be required.
对器官移植受者进行西罗莫司药物治疗的治疗监测及剂量个体化是标准的临床实践。由于缺乏免疫测定法，多年来西罗莫司监测受到限制。近期在IMx分析仪上重新引入的西罗莫司微粒酶免疫测定法（MEIA）有可能解决这一情况。本研究使用患者样本，将MEIA西罗莫司方法与既定的高效液相色谱-串联质谱法（HPLC-MS/MS）进行了比较。采用既定的HPLC-UV测定法进行独立交叉验证。对于质量控制材料（5、11、22μg/L），MEIA基于批内和批间精密度（CV）以及准确度（偏差）分别<8%和<13%，显示出可接受的验证标准。定量下限约为3μg/L。使用从各类器官移植受者获得的乙二胺四乙酸全血样本（n = 116），将免疫测定法的性能与HPLC-MS/MS进行比较。所得的戴明回归线为：MEIA = 1.3×HPLC-MS/MS + 1.3（r = 0.967，S(y/x) = 1），平均偏差为49.2%±23.1%（范围为-2.4%至128%；P<0.001）。本研究未探究偏差大且变化的原因，但西罗莫司代谢物与MEIA抗体的交叉反应性可能是一个重要的促成因素。虽然MEIA西罗莫司方法可能是移植受者西罗莫司剂量个体化的辅助手段，但使用者在解释结果时必须考虑到显著且变化的偏差所带来的影响。在出现复杂临床问题的特定患者中，可能需要参考特定的色谱方法。
