Administration study of somapacitan, a long-acting growth hormone derivative, in horse for doping control purpose.
Abstract: Somapacitan is the second generation of recombinant human growth hormone (rhGH) medication that retains the pharmacological effects of rhGH but exhibits a longer duration of action due to its reversible albumin-binding in the body. In general, the use of all recombinant growth hormone (rGH) analogues is banned by the human and animal sports regulatory authorities due to their anabolic and lipolytic effects. However, little is known about the elimination kinetics and biological effects of the newly introduced long-acting rhGH, somapacitan, in horses. This paper describes the administration study of somapacitan and its elimination in horses, its correlation with plasma insulin-like growth factor-1 (IGF-1) levels, an established indicator for rGH abuse, and the evaluation of the detection capability of our recently developed liquid chromatography high-resolution mass spectrometry (LC-HRMS) method in equine plasma after extraction and trypsin digestion specifically designed for controlling the misuse or abuse of somapacitan. Three thoroughbred mares were each administered 90 mg somapacitan subcutaneously. Plasma IGF-1 concentration significantly increased in all horses after administration of somapacitan. The somapacitan-specific T10 peptide fragment that allows discriminative identification of somapacitan and rhGH was detected up to 14 days and confirmed in post-administration samples collected up to 10 days. Several shared peptide fragments between somapacitan and rhGH were also detected and confirmed in plasma samples collected 14 days post-administration, supporting the applicability of the test strategy for the analysis of authentic doping control samples in horses.
Copyright © 2025 Elsevier Ltd. All rights reserved.
Publication Date: 2025-08-25 PubMed ID: 40886666DOI: 10.1016/j.ghir.2025.101662Google Scholar: Lookup
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Summary
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Overview
- This study investigated the administration, elimination, and detection of somapacitan, a long-acting growth hormone derivative, in horses, with the goal of improving doping control methods in equine sports.
Background and Purpose
- Somapacitan: A second-generation recombinant human growth hormone (rhGH) designed to have a longer action due to reversible binding to albumin in the bloodstream.
- Regulatory context: Recombinant growth hormones (rGH) and their analogues are banned substances in both human and animal sports for their anabolic (muscle-building) and lipolytic (fat-reducing) effects.
- Knowledge gap: Limited information exists about how somapacitan behaves in horses – specifically, how it is eliminated from the body and its biological effects, including insulin-like growth factor 1 (IGF-1) response.
- Study aim: To characterize somapacitan’s pharmacokinetics and biological impact in horses and develop effective detection methods to prevent doping.
Methodology
- Subjects: Three thoroughbred mares were selected for the study.
- Dosage and administration: Each horse was given a 90 mg subcutaneous injection of somapacitan.
- Biomarker measurement: Plasma levels of insulin-like growth factor 1 (IGF-1), a recognized indicator of rhGH activity, were monitored as an indirect measure of somapacitan’s biological effect.
- Detection technique: A specialized liquid chromatography high-resolution mass spectrometry (LC-HRMS) method was utilized:
- Plasma samples were processed with extraction and trypsin digestion.
- The method specifically identifies somapacitan by detecting unique peptide fragments such as the somapacitan-specific T10 peptide.
Results
- IGF-1 response: After somapacitan administration, plasma IGF-1 levels significantly increased in all three horses, confirming somapacitan’s biological activity in equines.
- Peptide detection: The somapacitan-specific T10 peptide fragment was detectable in plasma for up to 14 days post-administration.
- Confirmation after 10 days: The presence of this T10 peptide was confirmed in samples collected as late as 10 days post-injection, demonstrating a relatively long detection window.
- Detection of shared peptides: Peptide fragments common to both somapacitan and rhGH also were identified up to 14 days after administration, supporting the sensitivity and applicability of the LC-HRMS method for doping control.
Significance and Applications
- The study successfully demonstrated that somapacitan causes a measurable increase in IGF-1 levels in horses, which can serve as a biomarker for growth hormone abuse.
- The detection method developed is capable of specifically distinguishing somapacitan from other rhGH forms by identifying unique peptide signatures.
- The relatively long detection window (up to two weeks) supports the feasibility of monitoring somapacitan misuse in equine sports.
- This research provides foundational data and analytical tools to improve anti-doping efforts and ensure fair competition in horse racing and other animal sports.
Cite This Article
APA
Shimizu Y, Sugai-Bannai M, Tanabe H, Saito K, Ito H, Tokushige H, Kamiya K, Hirano-Kodaira M, Yamada M, Leung GN.
(2025).
Administration study of somapacitan, a long-acting growth hormone derivative, in horse for doping control purpose.
Growth Horm IGF Res, 82, 101662.
https://doi.org/10.1016/j.ghir.2025.101662 Publication
Researcher Affiliations
- Drug Analysis Department, Laboratory of Racing Chemistry, Tochigi, Japan. Electronic address: y-shimizu@lrc.or.jp.
- Drug Analysis Department, Laboratory of Racing Chemistry, Tochigi, Japan.
- Drug Analysis Department, Laboratory of Racing Chemistry, Tochigi, Japan.
- Drug Analysis Department, Laboratory of Racing Chemistry, Tochigi, 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.
- Anti-Doping Section, Equine Department, Japan Racing Association, 1-1-1 Nishishimbashi, Minato-ku, Tokyo 105-0003, Japan.
- Drug Analysis Department, Laboratory of Racing Chemistry, Tochigi, Japan.
- Drug Analysis Department, Laboratory of Racing Chemistry, Tochigi, Japan.
- Drug Analysis Department, Laboratory of Racing Chemistry, Tochigi, Japan.
MeSH Terms
- Horses
- Animals
- Doping in Sports / prevention & control
- Insulin-Like Growth Factor I / analysis
- Insulin-Like Growth Factor I / metabolism
- Substance Abuse Detection / methods
- Female
- Human Growth Hormone / administration & dosage
- Male
- Humans
Conflict of Interest Statement
Declaration of competing interest There are no conflicts to declare.
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