选择性雌激素受体调节剂他莫昔芬（TAM）广泛用于治疗雌激素受体阳性（ER+）乳腺癌女性患者。恩多西芬（ENDX）是TAM的有效代谢物，对TAM的临床活性非常重要。虽然已经发表了多篇有关TAM代谢的论文，但很少有研究对ENDX的代谢进行了检查或定量分析。为了定量测定患者血浆样品中的ENDX及其代谢物，我们开发并验证了快速、敏感、特异的液相色谱-串联质谱（LC-MS / MS）方法，用于定量测定E和Z异构体的ENDX（0.5-500 ng / ml）和ENDX代谢物的浓度，包括norendoxifen（分别为1-500和0.5-500 ng / ml E和Z）、ENDX儿茶酚（分别为3.075-307.5和1.92-192 ng / ml E和Z）、4'-羟基ENDX（分别为0.33-166.5和0.33-333.5 ng / ml E和Z）、ENDX甲氧基儿茶酚（分别为0.3-300和0.2-200 ng / ml E和Z）和ENDX葡萄糖醛酸酯（分别为2-200和3-300 ng / ml E和Z）。色谱分离采用HSS T3预柱和Poroshell 120 EC-C18分析柱，分别使用0.1%甲酸/水和0.1%甲酸/甲醇作为洗脱剂，后接MS / MS检测。分析时间为6.5分钟。标准曲线在浓度范围内呈线性（R2≥0.98）。所有物质的高、中、低质量控制浓度的日内和日间精密度和准确度都在可接受的范围内（85%到115%）。平均回收率均在90%以上。该方法已成功应用于每日口服Z-ENDX的一期临床研究的临床血浆样品。 版权所有©2023 Elsevier B.V.

The selective estrogen receptor modifier tamoxifen (TAM) is widely used for the treatment of women with estrogen receptor positive (ER+ ) breast cancer. Endoxifen (ENDX) is a potent, active metabolite of TAM and is important for TAM's clinical activity. While multiple papers have been published regarding TAM metabolism, few studies have examined or quantified the metabolism of ENDX. To quantify ENDX and its metabolites in patient plasma samples, we have developed and validated a rapid, sensitive, and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantitative determination of the E- and Z-isomers of ENDX (0.5-500 ng/ml) and the ENDX metabolites norendoxifen (1-500 and 0.5-500 ng/ml E and Z, respectfully), ENDX catechol (3.075-307.5 and 1.92-192 ng/ml E and Z, respectfully), 4'-hydroxy ENDX (0.33-166.5 and 0.33-333.5 ng/ml E and Z, respectfully), ENDX methoxycatechol (0.3-300 and 0.2-200 ng/ml E and Z, respectfully), and ENDX glucuronide (2-200 and 3-300 ng/ml E and Z, respectfully) in human plasma. Chromatographic separation was accomplished on a HSS T3 precolumn attached to an Poroshell 120 EC-C18 analytical column using 0.1 % formic acid/water and 0.1 % formic acid/methanol as eluents followed by MS/MS detection. The analytical run time was 6.5 min. Standard curves were linear (R2 ≥ 0.98) over the concentration ranges. The intra- and inter-day precision and accuracy, determined at high-, middle-, and low-quality control concentrations for all analytes, were within the acceptable range of 85 % and 115 %. The average percent recoveries were all above 90 %. The method was successfully applied to clinical plasma samples from a Phase I study of daily oral Z-ENDX.Copyright © 2023 Elsevier B.V. All rights reserved.