Use of the hyphenated LC-MS/MS technique and NMR/IR spectroscopy for the identification of exemestane stress degradation products during the drug development
PBN-AR
Instytucja
Sieć Badawcza Łukasiewicz - Instytut Farmaceutyczny
Informacje podstawowe
Główny język publikacji
angielski
Czasopismo
European Journal of Pharmaceutical Sciences (35pkt w roku publikacji)
ISSN
0928-0987
EISSN
Wydawca
ELSEVIER SCIENCE BV
DOI
URL
Rok publikacji
2017
Numer zeszytu
Strony od-do
389-401
Numer tomu
109
Link do pełnego tekstu
Identyfikator DOI
Liczba arkuszy
Słowa kluczowe
angielski
Exemestane
Stability indicating method
Forced degradation
Fragmentation pathway
LC-MS/MS
Impurity profile
Streszczenia
Język
angielski
Treść
Exemestane (6-Methyleneandrosta-1,4-diene-3,17-dione) active pharmaceutical ingredient (EE-3) was subjected to thermal, photolytic, oxidative, acidic and base stress conditions prescribed by the ICH (International Conference on Harmonization) guideline Q1A(R2). EE-3 was found to degrade in base, acidic and oxidative conditions. Eleven new degradation products of EE-3 were characterized by the LC-MS/MS technique. One of these impurities was isolated and identified by the LC-MS/MS, NMR and IR techniques. The LC-MS/MS studies were carried out to establish fragmentation pathways of EE-3 and its new impurity. Based on the results obtained from different spectroscopic studies, this impurity was characterized as 3-hydroxy-1,6-dimethyl-oestratetraen-(1, 3, 5(10), 6)-17-one (EE-3Z). The degradation pathway of EE-3 leading to the generation of eleven products was proposed and this has not been reported so far. The separation of EE-3 from its impurities (process-related and degradants) was achieved using a Gemini C18 column (150 mm × 4.6 mm × 3 μm) with gradient elution. The degradation products were well resolved from the main peak and its impurities, thus proving the method's stability and indicating power of the method. The method was validated according to the ICH guidelines for parameters such as specificity, limit of detection, limit of quantitation, precision, linearity, accuracy, robustness and system suitability.
Cechy publikacji
oryginalny artykuł naukowy
Inne
System-identifier
PX-5a941eb2d5de7465a8057de3
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