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首页> 外文期刊>Journal of Pharmaceutical and Biomedical Analysis: An International Journal on All Drug-Related Topics in Pharmaceutical, Biomedical and Clinical Analysis >Development and validation of an UPLC-MS/MS method for the quantification of tamoxifen and its main metabolites in human scalp hair
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Development and validation of an UPLC-MS/MS method for the quantification of tamoxifen and its main metabolites in human scalp hair

机译：开发和验证用于定量人头皮头发中他莫昔芬及其主要代谢物的UPLC-MS / MS方法

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The aim of this study was to validate an earlier developed high-performance highly sensitive ultra performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method for quantification of tamoxifen and its three main metabolites (N-desmethyl-tamoxifen, 4-hydroxy-tamoxifen and 4-hydroxy-N-desmethyl-tamoxifen) in scalp hair. This non-invasive method might, by segmental analysis of hair, be useful in the determination of the concentration of drugs and its metabolites overtime, which can be used to study a wide variety of clinical relevant questions. Hair samples (150-300 hair strands, cut as close to the scalp as possible from the posterior vertex region of the head) were collected from female patients taking tamoxifen 20 mg daily (n = 19). The analytes were extracted using a liquid-liquid extraction procedure with carbonate buffer at pH 8.8 and a mixture of n-hexane/isopropranol method, followed by UPLC-MS/MS chromatography, based on an earlier validated method. The calibration curves were linear in the range of 1.00-200 pmol for tamoxifen and N-desmethyl-tamoxifen, with lower limit of quantitation of 1.00 pmol and 0.100-20.0 pmol with lower limit of quantitation of 0.100 pmol for endoxifen and 4-hydroxy-tamoxifen. Assay performance was fair with a within-run and between-run variability less than 9.24 at the three quality control samples and less than 15.7 for the lower limit of quantitation. Importantly, a steep linear decline was observed from distal to proximal hair segments. Probably, this is due to UV exposure as we showed degradation of tamoxifen and its metabolites after exposure to UV-light. Furthermore, higher concentrations of tamoxifen were found in black hair samples compared to blond and brown hair samples. We conclude that measurement of the concentration of tamoxifen and its main metabolites in hair is possible, with the selective, sensitive, accurate and precise UPLC-MS/MS method. However, for tamoxifen, it seems not possible to determine exposure over time with segmental analysis of hair, probably largely due to the effect of UV irradiation. Further research should therefore focus on quantification of other anticancer drugs, in segmented scalp hair, that are less sensitive to UV irradiation. (C) 2015 Elsevier B.V. All rights reserved.
机译：这项研究的目的是验证一种较早开发的高性能高灵敏度超高效液相色谱/串联质谱（UPLC-MS / MS）方法，用于定量他莫昔芬及其三种主要代谢物（N-去甲基-他莫昔芬，4-头皮头发中的羟基-他莫昔芬和4-羟基-N-去甲基-他莫昔芬）。通过对头发进行分段分析，这种非侵入性方法可能有助于确定随时间推移的药物及其代谢产物的浓度，可用于研究各种临床相关问题。从每天服用他莫昔芬20 mg（n = 19）的女性患者中收集头发样本（150-300根发丝，从头部的后顶点区域切到尽可能靠近头皮的位置）。使用液-液萃取程序，pH 8.8的碳酸盐缓冲液和正己烷/异丙醇混合物的方法对分析物进行萃取，然后根据较早验证的方法进行UPLC-MS / MS色谱分析。他莫昔芬和N-去甲基他莫昔芬的校准曲线在1.00-200 pmol范围内是线性的，定量下限为1.00 pmol和0.100-20.0 pmol，endoxifen和4-hydroxy-他莫昔芬。测定性能是合理的，三个质量控制样品的批次内和批次间变异性小于9.24，定量下限小于15.7。重要的是，从远端到近端的头发段观察到陡峭的线性下降。可能是由于紫外线暴露，因为我们在暴露于紫外线后显示出他莫昔芬及其代谢产物的降解。此外，与金发和棕色头发样品相比，黑发样品中他莫昔芬的浓度更高。我们得出结论，使用选择性，灵敏，准确和精确的UPLC-MS / MS方法可以测量头发中他莫昔芬及其主要代谢物的浓度。但是，对于他莫昔芬，似乎无法通过头发的分段分析确定随时间变化的暴露量，这可能主要是由于紫外线辐射的影响。因此，进一步的研究应集中于定量头皮头发中对紫外线辐射较不敏感的其他抗癌药物的定量。 （C）2015 Elsevier B.V.保留所有权利。

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