Objective: To identify the related substances of progesterone sustained-release vaginal gel by liquid chromatography mass spectrometry (LC-MS). Methods: The separation was carried out on YMC-Triart C18 (150 mm×4.6 mm, 3 μm) column by gradient elution using acetonitrile and water as the mobile phases. The accurate mass and elemental composition of the parent ions and their product ions of related substances were determined by electrospray-ionization quadrupole time-of-flight high resolution mass spectrometry (ESI Q TOF MS) at collision energies of 5-45 eV. The structures of the related substances were identified by spectral analysis. Results: Under the established analytical condition, progesterone and its related substances were adequately separated, and 18 major related substances were detected and identified by hyphenated techniques in progesterone sustained-release vaginal gel and their stressed samples. Among them, 7 were the impurities listed in the EP or previous reported, and the others were unknown related substances identified for the first time in this paper. The established LC-MS technique was effective for the separation and identification of the related substances of progesterone sustained-release vaginal gel. Conclusion: Progesterone is unstable under acid, alkaline, and high-temperature stress conditions, and prone to produce oxidation degradants. The research results can provide a reference for the quality control of progesterone sustained-release vaginal gel.
HAO Jun-ju
,
CHEN Li
,
NING Man-ru
,
LU Yu-ting
,
SONG Min
,
HANG Tai-jun
. Structural identification of the related substances in progesterone sustained-release vaginal gel by LC-Q TOF MS[J]. Chinese Journal of Pharmaceutical Analysis, 2025
, 45(1)
: 135
-145
.
DOI: 10.16155/j.0254-1793.2024-0195
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