Abstract
The influence of pH, temperature, various buffer species at different concentrations, and ionic strength on the stability of gonadorelin and triptorelin in aqueous solution has been studied using stability-indicating high-performance liquid chromatographic methods. The degradation behavior of both peptides is similar. The maximum stability of both peptides was shown to be at an approximate pH of 5.0. Acetate has the most favorable effect on stability, while phosphate causes higher degradation. Varying the concentration of acetate buffer does not affect the degradation behavior of the peptides. A higher phosphate concentration in buffer solutions causes higher degradation, however. The ionic strength of buffer solutions has no significant influence on stability. Solutions of gonadorelin and triptorelin, respectively, buffered with acetate (0.1 M, pH 5.0) with 3% (w/v) mannitol as an additive show a predicted t 90% of 9.0 years and 7.7 years at 20°C, respectively.
Similar content being viewed by others
REFERENCES
A. V. Schally, A. Arimura, Y. Baba, R. M. G. Nair, H. Matsuo, T. W. Redding, L. Debeljuk, and W. F. White. Isolation and properties of the FSH and LH-releasing-hormone. Biochem. Biphys. Res. Commun. 43:393–399 (1971).
D. H. Coy, J. A. Vilchez-Martinez, E. J. Coy, and A. V. Schally. Analogs of luteinizing hormone-releasing hormone with increased biological activity produced by D-amino acid substitutions in position 6. J. Med. Chem. 19:423–425 (1976).
G. Forti. Clinical applications of GnRH analogs. J. Endocrinol. Invest. 11:745–754 (1988).
B. J. Furr and J. R. Woodburn. Luteinizing hormone-releasing hormone and its analogues: A review of biological properties and clinical uses. J. Endocrinol. Invest. 11:535–557 (1988).
R. N. Clayton. Gonadotrophin releasing hormone: From physiology to pharmacology. Clin. Endocrinol. 26:361–384 (1987).
R. J. Santen and J.-P. Bourguignon. Gonadotropin-releasing hormone: Physiological and therapeutic aspects, agonists and antagonists. Hormone Res. 28:88–103 (1987).
A. K. Banga and Y. W. Chien. Systemic delivery of therapeutic peptides and proteins. Int. J. Pharm. 48:15–50 (1988).
H. J. Roth. Polypeptide als Arzneistoffe. Dtsch. Apoth. Ztg. 128:1085–1102 (1988).
P. M. Hahn, D. A. Van Vugt, and R. L. Reid. The stability of synthetic gonadotropin-releasing hormone in solution. Fertil. Steril. 48:155–158 (1987).
D. M. Johnson, R. A. Pritchard, W. F. Taylor, D. Conley, G. Zuniga, and K. G. McGreevy. Degradation of the LH-RH analog nafarelin acetate in aqueous solution. Int. J. Pharm. 31:125–129 (1986).
Y.-F. Shi, R. J. Sherins, D. Brightwell, J. F. Galleli, and D. C. Chatterji. Long-term stability of aqueous solutions of luteinizing hormone-releasing hormone assessed by an in vitro bioassay and liquid chromatography. J. Pharm. Sci. 73:818–821 (1984).
J. Winterer, D. Chatterji, F. Comite, M. H. Decker, D. L. Loriaux, J. F. Galleli, and G. B. Cutler, Jr. Thermal stability of a long-acting analogue of luteinizing hormone-releasing hormone (D-Trp6-Pro9-Net-LHRH). Contraception 27:195–200 (1983).
D. C. Sertl, R. N. Johnson, and B. T. Kho. An accurate, specific HPLC method for the analysis of a decapeptide in a lactose matrix. J. Liq. Chromatogr. 4:1135–1156 (1981).
K. Nishi H, Ito, S. Shinagawa, C. Hatanaka, M. Fujino, and M. Hattori. In H. Yonehara (ed.), Peptide Chemistry 1979, Protein Research Foundation, Osaka, 1980, pp. 175–180.
J. Sandow, E. Vogl, and W. Bogie. Effect of storage on LH-RH. N. Engl. J. Med. 296:885 (1977).
W. C. Dermody and J. R. Reel. Effect of storage on LH-RH. N. Engl. J. Med. 295:173 (1976).
E. Debesis, J. P. Boehlert, T. E. Givand, and J. C. Sheridan. Submitting HPLC methods to the compendia and regulatory agencies. Pharm. Techn. 6:120–137 (1982).
J. W. van Nispen. In D. D. Breimer and P. Speiser (eds.), Topics in Pharmaceutical Sciences 1987, Elsevier Science, Amsterdam, 1987, pp. 293–307.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Helm, V.J., Müller, B.W. Stability of Gonadorelin and Triptorelin in Aqueous Solution. Pharm Res 7, 1253–1256 (1990). https://doi.org/10.1023/A:1015981704133
Issue Date:
DOI: https://doi.org/10.1023/A:1015981704133