Long-term stability of aqueous solutions of luteinizing hormone-releasing hormone assessed by an in vitro bioassay and liquid chromatography.

The stability of aqueous solutions of luteinizing hormone-releasing hormone (LHRH) after extended storage at various temperatures was investigated using a newly developed HPLC assay and an in vitro dispersed pituitary cell culture bioassay. Good correlations were obtained between the potency obtained by HPLC and bioassay in samples stored at 37 degrees C or subjected to different stress conditions. No significant decrease in activity of LHRH was observed in aqueous solutions stored at 37 degrees C for up to 10 weeks, at 4 degrees C for 2 years, or subjected to repeated freezing and thawing for 5 d. Heating to 60 degrees C in sterile pH 9.0 buffer up to 11 d and storage at ambient temperature in nonsterile solution for 4 months produced well-distinguished degradation products and a decrease in potency. It is concluded that sterile aqueous solutions of LHRH are stable for at least 10 weeks at 37 degrees C and, thus, could be reliably used for chronic administration when long-term stability at body temperature is important.