Murphy C, Fotsis T, Pantzar P, Adlercreutz H, Martin F
J Steroid Biochem. 1987 May;26(5):547-55. doi: 10.1016/0022-4731(87)90006-9.
A method for the analysis of tamoxifen and its metabolites in plasma from tamoxifen treated breast cancer patients, by capillary GC-MS using selected ion monitoring has been developed. Metabolite extraction was carried out on a Sep-pak C18 cartridge and metabolite purification by selective ion exchange chromatographic steps. Satisfactory recovery of radioactive standards through the extraction and purification steps was obtained. The method was shown to be accurate and precise with precision coefficient of variation values ranging from 4.3-11% for tamoxifen and its metabolites. Tamoxifen, 4-hydroxytamoxifen, metabolite Y and N-desmethyltamoxifen were identified with certainty in patient plasma on the basis of GC relative retention times and mass spectral comparison with authentic standards; because of their low abundance in plasma cis-metabolite E and 3,4-dihydroxytamoxifen could only be tentatively identified but identical GC behaviour and a satisfactory comparison of the abundance of key fragment ions was achieved. The tamoxifen and metabolite concentration ranges (ng X ml-1) in the group of patients who received 40 or 80 ng tamoxifen for 14 days were tamoxifen, 307-745; N-desmethyltamoxifen, 185-491; 4-hydroxytamoxifen, 1.4-2.5; 3,4-dihydroxytamoxifen, 0.7-2.0; metabolite Y, 19.0-112; and metabolite E1, 0.9-2.0.
已开发出一种通过使用选择离子监测的毛细管气相色谱 - 质谱法分析他莫昔芬治疗的乳腺癌患者血浆中他莫昔芬及其代谢物的方法。代谢物提取在Sep - pak C18柱上进行，并通过选择性离子交换色谱步骤进行代谢物纯化。通过提取和纯化步骤获得了放射性标准品的满意回收率。该方法被证明准确且精确，他莫昔芬及其代谢物的精密度变异系数值范围为4.3 - 11%。根据气相色谱相对保留时间以及与标准品的质谱比较，在患者血浆中明确鉴定出了他莫昔芬、4 - 羟基他莫昔芬、代谢物Y和N - 去甲基他莫昔芬；由于它们在血浆中的丰度较低，顺式代谢物E和3,4 - 二羟基他莫昔芬只能初步鉴定，但实现了相同的气相色谱行为以及关键碎片离子丰度的满意比较。在接受40或80 ng他莫昔芬治疗14天的患者组中，他莫昔芬及其代谢物的浓度范围（ng X ml-1）为：他莫昔芬，307 - 745；N - 去甲基他莫昔芬，185 - 491；4 - 羟基他莫昔芬，1.4 - 2.5；3,4 - 二羟基他莫昔芬，0.7 - 2.0；代谢物Y，19.0 - 112；以及代谢物E1，0.9 - 2.0。
