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应用两种卡马西平免疫分析法建立的数学方程估算血浆中卡马西平和卡马西平-10,11-环氧化物的浓度。

Estimation of carbamazepine and carbamazepine-10,11-epoxide concentrations in plasma using mathematical equations generated with two carbamazepine immunoassays.

机构信息

Department of Pathology and Laboratory Medicine, University of Texas-Houston Medical School, Houston, TX 77030, USA.

出版信息

Am J Clin Pathol. 2010 May;133(5):728-36. doi: 10.1309/AJCPFAHVB26VVVTE.

Abstract

Carbamazepine is metabolized to an active metabolite known as carbamazepine-10,11-epoxide, or simply the "epoxide" metabolite. The presence of this metabolite can have clinically significant implications in therapeutic drug monitoring of carbamazepine, but accurate quantification of the epoxide metabolite is currently limited to chromatographic techniques. In this study, mathematical equations are proposed for the estimation of carbamazepine and epoxide metabolite concentrations based on values generated by common carbamazepine immunoassays. Three immunoassays were studied: particle-enhanced turbidimetric inhibition immunoassay (PETINIA, Siemens Healthcare Diagnostics, Deerfield, IL), ADVIA Centaur (Siemens Healthcare Diagnostics), and a cloned enzyme donor immunoassay (CEDIA; Roche, Indianapolis, IN). Equations were based on observed cross-reactivity of epoxide with the PETINIA (average, 96.2%; range, 86.6%-105.7%) and epoxide cross-reactivity with the ADVIA Centaur assay (average, 6.5%; range, 5.3%-7.7%). In addition, equations were developed using average cross-reactivity of epoxide with the PETINIA and with the CEDIA. Values determined by calculation correlated well with carbamazepine and epoxide concentrations in supplemented and patient samples, for which values of carbamazepine (2.2-12.0 microg/mL [9-51 micromol/L]) and the epoxide metabolite (0.6-2.4 microg/mL) were also verified by liquid chromatography-tandem mass spectrometry.

摘要

卡马西平代谢为一种活性代谢物,称为卡马西平-10,11-环氧化物,或简称“环氧化物”代谢物。这种代谢物的存在对卡马西平的治疗药物监测具有重要的临床意义,但目前对环氧化物代谢物的准确定量仅限于色谱技术。在这项研究中,根据常见卡马西平免疫分析产生的值,提出了估算卡马西平和环氧化物代谢物浓度的数学方程。研究了三种免疫分析:颗粒增强比浊抑制免疫分析(PETINIA,西门子医疗诊断,迪尔菲尔德,IL)、ADVIA Centaur(西门子医疗诊断)和克隆酶供体免疫分析(CEDIA;罗氏,印第安纳波利斯,IN)。方程基于观察到的环氧化物与 PETINIA 的交叉反应(平均为 96.2%;范围为 86.6%-105.7%)和环氧化物与 ADVIA Centaur 测定的交叉反应(平均为 6.5%;范围为 5.3%-7.7%)。此外,还使用环氧化物与 PETINIA 和 CEDIA 的平均交叉反应性开发了方程。计算得出的值与补充和患者样本中的卡马西平和环氧化物浓度密切相关,其中卡马西平(2.2-12.0 microg/mL [9-51 micromol/L])和环氧化物代谢物(0.6-2.4 microg/mL)的值也通过液相色谱-串联质谱法得到验证。

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