Chlortalidone (CLT) is a thiazide‐type diuretic with high affinity for the erythrocyte carbonic anhydrase. Therapeutically, it is mostly used to treat edema and hypertension due to liver cirrhosis, heart insufficiency, or renal dysfunction. Although diuretics and masking agents are prohibited by the World Anti‐Doping Agency (WADA) at all times in sports, substances belonging to this category are constantly detected in athlete samples, according to WADA's annual testing figures. Within this group of structurally diverse compounds, a threshold of 20 ng/mL has been introduced for six substances solely due to their presence as contaminants in other permitted drugs because of pharmaceutical production processes. In a recent presumptive doping case with a low urinary CLT concentration, the question of unintentional doping, for example, by contaminated non‐steroidal anti‐inflammatory drug intake, arose. To examine this potential scenario, a co‐elimination of low‐dose CLT and hydrochlorothiazide (HCTA; 20 × 50 μg, 0.2 mg/day each) was conducted on five consecutive days in two volunteers. Urine samples were subjected to liquid chromatography‐tandem mass spectrometry (LC–MS/MS). Moreover, we examined the incorporation of CLT in scalp hair. HCTA is rapidly excreted renally in comparatively high concentrations. In contrast, the elimination of CLT is considerably slower (terminal elimination half‐life extended by a factor of 12) and, consequently, much less concentrated in corresponding urine samples (45 and 53 ng/mL, respectively). Conversely, a higher hair incorporation of chlorthalidone was observed with simultaneous dosing of both. The results suggest that an unintentional intake of sub‐therapeutic CLT doses due to contamination might result in an adverse analytical finding.

中文翻译：

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低剂量氯噻酮的消除曲线及其在头发中的检测以进行兴奋剂分析——对无意非治疗性暴露的影响

氯他利酮 (CLT) 是一种噻嗪类利尿剂，对红细胞碳酸酐酶具有高亲和力。在治疗上，主要用于治疗肝硬化、心功能不全或肾功能不全引起的水肿和高血压。尽管世界反兴奋剂机构 (WADA) 在体育运动中始终禁止使用利尿剂和掩蔽剂，但根据世界反兴奋剂机构的年度检测数据，运动员样本中不断检测到属于此类的物质。在这组结构多样的化合物中，有 6 种物质引入了 20 ng/mL 的阈值，这仅仅是因为它们在制药生产过程中作为污染物存在于其他允许的药物中。在最近的一起尿 CLT 浓度较低的疑似兴奋剂案件中，出现了无意服用兴奋剂的问题，例如摄入受污染的非甾体抗炎药。为了检查这种潜在情况，两名志愿者连续五天联合消除低剂量 CLT 和氢氯噻嗪（HCTA；20 × 50 μg，各 0.2 mg/天）。对尿液样本进行液相色谱-串联质谱（LC-MS/MS）分析。此外，我们还检查了 CLT 在头皮毛发中的掺入情况。HCTA 以相对较高的浓度快速经肾排泄。相比之下，CLT 的消除速度相当慢（最终消除半衰期延长了 12 倍），因此相应尿液样本中的浓度要低得多（分别为 45 ng/mL 和 53 ng/mL）。相反，同时给药时观察到氯噻酮的头发掺入量更高。结果表明，由于污染而无意摄入低于治疗剂量的 CLT 可能会导致不利的分析结果。