Vadadustat is a newly launched hypoxia-inducible factor stabilizer with anti-anemia and erythropoietic effects; however, its use in horses is expressly forbidden in both racing and equestrian competitions. Following our previous report on the pharmacokinetic study of vadadustat in horse plasma and urine, a long-term longitudinal analysis of vadadustat in horse hair after nasoesophageal administration (3 g/day for 3 days) to three thoroughbred mares is described in this study. Our main objective is to further extend the detection period of vadadustat for the purpose of doping control. Three bunches of mane hair from each horse were collected at 0 (pre), 1, 2, 3 and 6 month(s) post-administration. These hair samples were each cut into 2-cm segments and pulverized after decontamination of hair samples. The analyte in the powdered hair samples was extracted with liquid-liquid extraction followed by further purification by solid-phase extraction with strong anion exchange columns. The amount of vadadustat incorporated into the hair was quantified with a newly developed and validated method using liquid chromatography-high-resolution mass spectrometry. Our results show that vadadustat was confirmed in all post-administration hair samples, but its metabolites were not present. Thus, the detection window for vadadustat could be successfully extended up to 6 months post-administration. Interestingly, the 2-cm segmental analysis revealed that the tip of the drug band in the hair shifted along with the hair shafts in correspondence with the average hair growth rate (∼2.5 cm/month) but gradually diffused more widely from 2 cm at 1 month post-administration to up to 14 cm at 6 months post-administration. However, the loss in the total amount of vadadustat in hair over time was observed to most likely be due to the degradation of vadadustat. These findings will be useful for the control of abuse and/or misuse of vadadustat and the interpretation of positive doping cases.

中文翻译：

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以兴奋剂控制为目的对马毛中 vadadustat 进行分段分析和长期监测。

Vadadustat是新推出的缺氧诱导因子稳定剂，具有抗贫血和红细胞生成作用；然而，在赛马和马术比赛中明确禁止将其用于马匹。继我们之前关于马血浆和尿液中 vadadustat 的药代动力学研究报告之后，本研究描述了对三匹纯种母马经鼻食管给药（3 g/天，持续 3 天）后马毛中 vadadustat 的长期纵向分析。我们的主要目标是进一步延长vadadustat的检测周期，以达到兴奋剂控制的目的。在施用后0（前）、1、2、3和6个月从每匹马收集三束鬃毛。将这些毛发样本分别切成2厘米的片段并在毛发样本去污后粉碎。采用液-液萃取法提取粉末状毛发样品中的分析物，然后通过强阴离子交换柱进行固相萃取进一步纯化。使用液相色谱-高分辨率质谱法，采用新开发和验证的方法对掺入头发中的 vadadustat 量进行定量。我们的结果表明，所有给药后头发样本中都证实了 vadadustat，但其代谢物不存在。因此，vadadustat 的检测窗口可以成功延长至给药后 6 个月。有趣的是，2厘米分段分析显示，头发中药物带的尖端随着头发干的移动，与平均头发生长速率（~2.5厘米/月）相对应，但在1时从2厘米开始逐渐扩散得更广泛。给药后 6 个月时，身高可达 14 厘米。然而，观察到头发中瓦达司他总量随着时间的推移而减少，很可能是由于瓦达司他的降解。这些发现将有助于控制 vadadustat 的滥用和/或误用以及兴奋剂阳性案件的解释。