Clomiphene or clomifene is a selective estrogen receptor modulator (SERM), used to treat female fertility in case of ovulatory dysfunction. In sport, clomiphene is prohibited at all times for use by athletes and is listed in the section S4.2 (hormone and metabolic modulators) by the World Anti-Doping Agency (WADA). Indeed, clomiphene can indirectly increase testosterone levels in the body and can mitigate some side effects of synthetic steroid abuse. Despite its prescription to millions of subjects, its detection in human hair or nail clippings has never been reported. The aim of this study was to develop a specific method to identify clomiphene in hair and nail clippings by LC–MS-MS. The procedure was then applied in a case of challenged doping results. The method involves sonication/incubation for 1 hour of 30 mg of pulverized material in 1 mL of methanol in presence of 2 ng diazepam-d5 used as internal standard. The chromatographic separation was performed using a HSS C18 column with a 15 min gradient elution. After spiking blank hair and nail with the corresponding amounts of clomiphene, linearity was verified from 1 to 500 pg/mg (r² = 0.9994 and 0.9995 for hair and nail, respectively). The limit of detection was estimated at 0.3 pg/mg for both matrices. No interference was noted from endogenous compounds, particularly steroids. Clomiphene was identified at 85 and 20 pg/mg in the pubic hair and the fingernail clippings, respectively, of a male athlete challenging an adverse analytical finding.

中文翻译：

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角质基质（头发和指甲）中克罗米芬的检测

克罗米芬或克罗米芬是一种选择性雌激素受体调节剂 (SERM)，用于治疗排卵功能障碍的女性生育能力。在体育运动中，运动员在任何时候都禁止使用克罗米芬，并被世界反兴奋剂机构 (WADA) 列入 S4.2 部分（激素和代谢调节剂）。事实上，克罗米芬可以间接增加体内睾酮水平，并可以减轻合成类固醇滥用的一些副作用。尽管它已被数以百万计的受试者使用，但从未报道过在人类头发或指甲剪中检测到它。本研究的目的是开发一种通过 LC-MS-MS 识别头发和指甲剪中克罗米芬的具体方法。然后，该程序被应用于兴奋剂结果受到质疑的情况。该方法包括在 2 ng 地西泮-d5 用作内标的情况下，将 30 mg 粉碎材料在 1 mL 甲醇中超声处理/孵育 1 小时。使用HSS C18柱进行色谱分离，梯度洗脱15分钟。在空白头发和指甲中加入相应量的克罗米芬后，验证了 1 至 500 pg/mg 的线性（头发和指甲的 r² 分别为 0.9994 和 0.9995）。两种基质的检测限估计为 0.3 pg/mg。没有注意到内源性化合物，特别是类固醇的干扰。在一名对不利分析结果提出质疑的男性运动员的阴毛和指甲剪中，克罗米芬含量分别为 85 皮克/毫克和 20 皮克/毫克。