Department of Pharmacy & Pharmacology, Slotervaart Hospital/The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Breast Cancer Res Treat. 2012 Jun;133(2):793-8. doi: 10.1007/s10549-012-2000-1. Epub 2012 Mar 3.
The antiestrogenic effect of tamoxifen is mainly attributable to the active metabolites endoxifen and 4-hydroxytamoxifen. This effect is assumed to be concentration-dependent and therefore quantitative analysis of tamoxifen and metabolites for clinical studies and therapeutic drug monitoring is increasing. We investigated the large discrepancies in reported mean endoxifen and 4-hydroxytamoxifen concentrations. Two published LC-MS/MS methods are used to analyse a set of 75 serum samples from patients treated with tamoxifen. The method from Teunissen et al. (J Chrom B, 879:1677-1685, 2011) separates endoxifen and 4-hydroxytamoxifen from other tamoxifen metabolites with similar masses and fragmentation patterns. The second method, published by Gjerde et al. (J Chrom A, 1082:6-14, 2005) however lacks selectivity, resulting in a factor 2-3 overestimation of the endoxifen and 4-hydroxytamoxifen levels, respectively. We emphasize the use of highly selective LC-MS/MS methods for the quantification of tamoxifen and its metabolites in biological samples.
他莫昔芬的抗雌激素作用主要归因于其活性代谢物(endoxifen 和 4-羟基他莫昔芬)。这种作用被认为是浓度依赖性的，因此，为了进行临床研究和治疗药物监测，对他莫昔芬及其代谢物进行定量分析的需求日益增加。我们研究了报告的平均 endoxifen 和 4-羟基他莫昔芬浓度之间存在的巨大差异。使用两种已发表的 LC-MS/MS 方法分析了一组 75 例接受他莫昔芬治疗的患者的血清样本。Teunissen 等人的方法（J Chrom B，879:1677-1685, 2011）可将 endoxifen 和 4-羟基他莫昔芬与其他具有相似质量和碎片模式的他莫昔芬代谢物分离。然而，第二个由 Gjerde 等人发表的方法（J Chrom A，1082:6-14, 2005）缺乏选择性，导致 endoxifen 和 4-羟基他莫昔芬水平分别高估了 2-3 倍。我们强调在生物样本中定量分析他莫昔芬及其代谢物时使用高选择性的 LC-MS/MS 方法。
