Superiority of gas chromatography/tandem mass spectrometry assay (GC/MS/MS) for estradiol for monitoring of aromatase inhibitor therapy
Superiority of gas chromatography/tandem mass spectrometry assay (GC/MS/MS) for estradiol for monitoring of aromatase inhibitor therapy
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DOI：
10.1016/j.steroids.2007.05.003
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发表时间：
2007-07-01
期刊：
影响因子：
2.7
通讯作者：
Wang, Shuping
中科院分区：
文献类型：
--
作者：
Santen, Richard J.;Demers, Lawrence;Wang, Shuping
目前可用的血清雌二醇放射免疫测定方法缺乏足够的灵敏度和精确度，以监测放置在第三代芳香酶抑制剂的患者的雌二醇水平。我们最近验证了气相色谱/串联质谱法（GC/MS/MS）测定雌二醇和测定雌激素水平在正常绝经后妇女和乳腺癌妇女之前和期间的芳香化酶抑制剂管理。人血浆和人血清中GC/MS/MS测定的验证包括测定灵敏度（< 0.63 pg/ml）、精密度（所有CV均小于17.8%）、回收率（98-103%）和回收率线性（R = 0.998）。在所有条件下，与RIA相比，GC/MS/MS测定雌二醇水平较低（7.26 +/- 4.82 pg/ml对比正常绝经后妇女中的11.9 ± 12.0 pg/ml; 5.88 +/- 3.43 pg/ml对比治疗前乳腺癌患者中的13.8 +/- 7.5 pg/ml;和< 0.63 pg/ml，芳香酶抑制剂治疗期间为5.8 +/-4.1 pg/ml）。55名接受阿他美坦/托瑞米芬或来曲唑/安慰剂治疗的妇女在治疗4周、8周和12周时监测雌二醇水平。芳香化酶抑制剂治疗期间雌二醇的平均水平为5.8 +/- 4.1 pg/ml，通过RIA测定，GC/MS/MS测定< 0.63 pg/ml。通过RIA测定的芳香化酶抑制剂的抑制程度为58%，而GC/MS测定> 89%。这些结果表明，大多数RIA方法检测交叉反应的雌激素代谢物，并产生比GC/MS/MS更高的测定水平。几个药理学和临床的考虑表明，GC/MS/MS应成为监测芳香酶抑制剂治疗的首选方法。(C)2007爱思唯尔公司All rights reserved.
Currently available radioimmunoassay methods for estradiol in serum lack sufficient sensitivity and precision to monitor estradiol levels in patients placed on third generation aromatase inhibitors. We recently validated a gas chromatography/tandem mass spectrometry assay (GC/MS/MS) for estradiol and determined estrogen levels in normal post-menopausal women and in women with breast cancer before and during administration of aromatase inhibitors. Validation of the GC/MS/MS assay in human plasma and human serum included determination of assay sensitivity (< 0.63 pg/ml), precision (all CVs less than 17.8%), recovery (98-103%), and linearity of recovery (R = 0.998). Levels of estradiol were lower when assayed by GC/MS/MS compared to RIA under all conditions (7.26 +/- 4.82 pg/ml versus 11.9 + 12.0 pg/ml in normal post-menopausal women; 5.88 +/- 3.43 pg/ml versus 13.8 +/- 7.5 pg/ml in breast cancer patients prior to treatment; and < 0.63 pg/ml versus 5.8 +/- 4.1 pg/ml during aromatase inhibitor therapy). Fifty-five women treated either with atamestane/toremiphene or letrozole/placebo were monitored for estradiol levels at 4, 8 and 12 weeks of therapy. The mean levels of estradiol during aromatase inhibitor therapy was 5.8 +/- 4.1 pg/ml as measured by RIA and < 0.63 pg/ml by GC/MS/MS. The degree of suppression with the aromatase inhibitors as detected by RIA was 58% versus > 89% by GC/MS. These results suggest that most RIA methods detect cross-reacting estrogen metabolites and yield higher measured levels than GC/MS/MS. Several pharmacological and clinical considerations suggest that GC/MS/MS should become the preferred method for monitoring aromatase inhibitor therapy. (C) 2007 Elsevier Inc. All rights reserved.