Proposed Method for Mass Spectrometric Measurement of the Gonadotropin-Releasing Hormone Agonist Deslorelin.
4 affiliations
- 1Department of Comparative Medicine and Integrative Biology, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
- 2Pathobiology & Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
- 3Michigan State University Veterinary Diagnostic Laboratory, Section of Toxicology, College of Veterinary Medicine, Michigan State University, 4125 Beaumont Rd, East Lansing, MI 48910, USA.
- 4Michigan State University Veterinary Diagnostic Laboratory, Section of Bacteriology, Michigan State University, East Lansing, MI 48910, USA.
Abstract
Deslorelin (C₆₄H₈₃N₁₇O₁₂) is a peptide GnRH agonist drug with monoisotopic mass 1281.64 Da applied as a drug-releasing implant in veterinary medicine for promoting ovulation and male/female contraception. Despite relative safety, it is suspected of reproductive toxicity and potential harm to unborn or breast-fed children. The compound was designed for high potency and prolonged half-life making it difficult to measure quantitatively in serum. A deslorelin LC-MS/MS method relies on detecting unmetabolized undegraded intact peptide, a crucial consideration since certain metabolites are thought to have activity. We propose a method for analyzing deslorelin indirectly by cleaving a unique portion of the carboxy terminus containing the modified proline ProNHEt (N-ethyl-2-pyrrolidine carboxamide), which can be removed by Clostridiopeptidase specific for arginine bonds. ProNHEt can be extracted from digested serum, reacted to an N-t-butyldimethylsilyl derivative and analyzed by GC-MS/MS. Settings were optimized for detectability to <1 ppb, and derivatization gave maximum yields by adjustment of solvent, reaction time, temperature and additives. MALDI-TOF applied to deslorelin revealed binding by copper. The proposed method can be used to measure deslorelin in serum samples from various zoo and small animals. Detection of deslorelin by examination of released ProNHEt is proposed to have applicability to other GnRH superagonists such as triptorelin and deslorelin breakdown products that exhibit the ProNHEt structure.
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BibTeX
@article{wei2026proposed,
title = {{Proposed Method for Mass Spectrometric Measurement of the Gonadotropin-Releasing Hormone Agonist Deslorelin.}},
author = {Christine Wei and John P Buchweitz and Rinosh Mani and Dalen Agnew and Andreas F Lehner},
journal = {Toxics},
year = {2026},
month = oct,
doi = {10.3390/toxics14100913},
url = {https://europepmc.org/article/MED/42931700},
note = {CC BY},
}
RIS
TY - JOUR
TI - Proposed Method for Mass Spectrometric Measurement of the Gonadotropin-Releasing Hormone Agonist Deslorelin.
AU - Christine Wei
AU - John P Buchweitz
AU - Rinosh Mani
AU - Dalen Agnew
AU - Andreas F Lehner
PY - 2026
DA - 2026/10/16
JO - Toxics
DO - 10.3390/toxics14100913
UR - https://europepmc.org/article/MED/42931700
AB - Deslorelin (C₆₄H₈₃N₁₇O₁₂) is a peptide GnRH agonist drug with monoisotopic mass 1281.64 Da applied as a drug-releasing implant in veterinary medicine for promoting ovulation and male/female contraception. Despite relative safety, it is suspected of reproductive toxicity and potential harm to unborn or breast-fed children. The compound was designed for high potency and prolonged half-life making it difficult to measure quantitatively in serum. A deslorelin LC-MS/MS method relies on detecting unmetabolized undegraded intact peptide, a crucial consideration since certain metabolites are thought to have activity. We propose a method for analyzing deslorelin indirectly by cleaving a unique portion of the carboxy terminus containing the modified proline ProNHEt (N-ethyl-2-pyrrolidine carboxamide), which can be removed by Clostridiopeptidase specific for arginine bonds. ProNHEt can be extracted from digested serum, reacted to an N-t-butyldimethylsilyl derivative and analyzed by GC-MS/MS. Settings were optimized for detectability to <1 ppb, and derivatization gave maximum yields by adjustment of solvent, reaction time, temperature and additives. MALDI-TOF applied to deslorelin revealed binding by copper. The proposed method can be used to measure deslorelin in serum samples from various zoo and small animals. Detection of deslorelin by examination of released ProNHEt is proposed to have applicability to other GnRH superagonists such as triptorelin and deslorelin breakdown products that exhibit the ProNHEt structure.
SN - 2305-6304
ER -