Detection of the GH analogue somatrogon in doping control urine samples by means of LC-HRMS/MS

Somatrogon is a synthetic growth hormone (GH) analog, whose misuse in sports is prohibited at all times. As analytical approaches complementary to existing immunological GH detection methods were considered beneficial for its detection in doping control serum samples, a sensitive and specific qualitative mass spectrometric assay was recently developed, comprehensively characterized, and successfully employed to analyze authentic in vivo study samples. Within this follow-up project, this approach based on affinity purification, tryptic digestion, and LC-HRMS/MS was modified by implementing an additional ultrafiltration step to allow for the extraction of the intact drug and/or its metabolites from urine. Method validation demonstrated its specificity and sensitivity (LOD: 1 ng/mL), and the subsequent analysis of post-administration urine samples showed for the first time that intact (or at least GH receptor binding) somatrogon is excreted into urine and can be detected in most subjects for at least 96 h following injection. Consequently, anti-doping laboratories can also use urine to confirm the presence of somatrogon in athletes, where the GH differential isoform assay yielded atypical results in the corresponding serum specimens. Moreover, the latter assay also proved to be valuable as screening tool for the identification of urine samples potentially containing the GH analog.