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.