Segmental analysis and long-term monitoring of vadadustat in equine hair for the purpose of doping control.
Abstract: 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.
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Publication Date: 2023-08-18 PubMed ID: 37632695DOI: 10.1093/jat/bkad057Google Scholar: Lookup
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Summary
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The study is about an advanced method to detect the presence of a prohibited drug, vadadustat, in competition horses using the analysis of hair samples, extending the detection period up to 6 months after administration.
Objective and Methodology
- The main aim of the research paper is to extend the detection period of vadadustat, a drug with anti-anemia and erythropoietic effects prohibited in horse racing and equestrian competitions.
- The researchers used nasal delivery to administer vadadustat to three thoroughbred mares and tracked the presence of the drug in their hair over a period of six months, with samples collected at 0 (before administration), 1, 2, 3, and 6 months.
- Segments of mane hair from each horse were first decontaminated, processed into a powder, and then subjected to a series of extractions to isolate the drug residue.
- The amount of vadadustat was quantified using a method specifically developed for this purpose, involving liquid chromatography and high-resolution mass spectrometry.
Findings
- Vadadustat was present in all hair samples collected after the drug was administered. However, its metabolites were not detected.
- They successfully extended the detection window for vadadustat, demonstrating it could be traced in the hair up to six months post-administration.
- With segmental hair analysis, they observed that the ‘drug band’ (area with drug residues) in the hair shifted according to the average hair growth rate and diffused more widely over time.
- The total amount of vadadustat detected in the hair decreased over time, attributed to the degradation of the drug.
Implications
- The findings offer a new, more effective technique to detect the presence of vadadustat in competition horses, providing a longer window of detection than previous methods.
- Through understanding the pattern of drug movement and degradation in the hair, investigators can better interpret positive doping cases and implement appropriate controls.
Cite This Article
APA
Ishii H, Shibuya M, Kusano K, Sone Y, Kamiya T, Wakuno A, Ito H, Miyata K, Yamada M, Leung GN.
(2023).
Segmental analysis and long-term monitoring of vadadustat in equine hair for the purpose of doping control.
J Anal Toxicol, bkad057.
https://doi.org/10.1093/jat/bkad057 Publication
Researcher Affiliations
- Drug Analysis Department, Laboratory of Racing Chemistry, 1731-2 Tsuruta-machi, Utsunomiya, Tochigi 320-0851, Japan.
- Department of Pharmaceutical Sciences, Tohoku University Hospital, 1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8574, Japan.
- Drug Analysis Department, Laboratory of Racing Chemistry, 1731-2 Tsuruta-machi, Utsunomiya, Tochigi 320-0851, Japan.
- Veterinarian Section, Equine Department, Japan Racing Association, 6-11-1 Roppongi, Minato-ku, Tokyo 105-0003, Japan.
- Veterinarian Section, Equine Department, Japan Racing Association, 6-11-1 Roppongi, Minato-ku, Tokyo 105-0003, Japan.
- Equine Veterinary Clinic, Horse Racing School, Japan Racing Association, 835-1 Ne, Shiroi, Chiba 270-1431, Japan.
- Equine Veterinary Clinic, Horse Racing School, Japan Racing Association, 835-1 Ne, Shiroi, Chiba 270-1431, Japan.
- Equine Veterinary Clinic, Horse Racing School, Japan Racing Association, 835-1 Ne, Shiroi, Chiba 270-1431, Japan.
- Equine Veterinary Clinic, JRA Equestrian Park Utsunomiya Office, 321-4 Tokamicho, Utsunomiya, Tochigi 320-0856, Japan.
- Drug Analysis Department, Laboratory of Racing Chemistry, 1731-2 Tsuruta-machi, Utsunomiya, Tochigi 320-0851, Japan.
- Drug Analysis Department, Laboratory of Racing Chemistry, 1731-2 Tsuruta-machi, Utsunomiya, Tochigi 320-0851, Japan.
Grant Funding
- JRA 2022 / Japan Racing Association
- JRA 2022 / Japan Racing Association
Citations
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