Objective: To study the in vivo and in vitro activities of triptorelin related substances in its sustained-release injections,to develop accumulated data and provide strategies for the control of impurities and their limits. Methods: Cell Titer-Glo ATP fluorescence activity detection method was used to determine the inhibitory effect of triptorelin-related substances on the proliferation of prostate cancer cells LNCaP FGC. The HPLC-MS/MS method was used to determine the inhibitory effect of triptorelin-related substances on the level of testosterone in rat plasma. Results: Triptorelin free acid, triptorelin glycolate, and triptorelin diglycolate could inhibit the proliferation of prostate cancer cells, and the inhibition rates were 121%, 89% and 77% of that of triptorelin, respectively. Triptorelin glycolate, triptorelin diglycolate and acylated triptorelin could inhibit testosterone in rats to castrate levels, that was ≤0.5 ng·mL-1. Conclusion: Triptorelin free acid, triptorelin glycolate, triptorelin diglycolate, and acylated triptorelin have pharmacological activities comparable to triptorelin.
SUN Yue, GUO Ning-zi, YANG Hua-xin, LI Zhan-jun, HU Xin-yue, XU Ke-zheng, LIANG Cheng-gang
. Comparative analysis on the activities of impurity in triptorelin sustained-release injection*[J]. Chinese Journal of Pharmaceutical Analysis, 2022
, 42(9)
: 1546
-1553
.
DOI: 10.16155/j.0254-1793.2022.09.07
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