Identification of new impurities of enalapril maleate on oxidation in the presence of magnesium monoperoxyphthalate.
Stress stability testing and forced degradation were used to determine the stability of enalapril maleate (EM) and to find a degradation pathway for the drug. The degradation impurities, formed under different stressed conditions, were investigated by HPLC and UPLC-MS methods. HPLC analysis showed several degradation impurities of which several were already determined, but on oxidation in the presence of magnesium monoperoxyphthalate (MMPP) several impurities of EM were observed which were not yet characterized. The HPLC methods for determination of EM were validated. The linearity of HPLC method was established in the concentration range between 0.5 and 10 microg/mL with correlation coefficient greater than 0.99. The LOD of EM was 0.2 microg/mL and LOQ was 0.5 microg/mL. The validated HPLC method was used to determine the degradation impurities in samples after stress stability testing and forced degradation of EM. In order to identify new degradation impurities of EM after forced degradation UPLC-MS/MS(n), Orbitrap has been used. It was found that new impurities are oxidation products: (S)-1-((S)-2-((S)-1-ethoxy-4-(o,m,p-hydroxyphenyl)-1-oxobutan-2-ylamino)propanoyl)pyrrolidine-2-carboxylic acid, (2S)-1-((2S)-2-((2S)-1-ethoxy-4-hydroxy-1-oxo-4-phenylbutan-2-ylamino)propanoyl)pyrrolidine-2-carboxylic acid. (S)-2-(3-phenylpropylamino)-1-(pyrrolidin-1-yl)propan-1-one was identified as a new degradation impurity.
Toporisic
Rebeka
R
Krka, dd, Smarjeska cesta 6, 8501 Novo mesto, Slovenia. rebeka.toporisic@krka.biz
Mlakar
Anita
A
Hvala
Jernej
J
Prislan
Iztok
I
Zupancic-Kralj
Lucija
L
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000032:analysis* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004340:Drug Contamination; D004355:Drug Stability; D004656:Enalapril / Q000032:analysis* / Q000737:chemistry; D006358:Hot Temperature; D006813:Humidity; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010795:Phthalic Acids / Q000737:chemistry*; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods; D013678:Technology, Pharmaceutical / Q000379:methods; D013997:Time Factors
D000806:Angiotensin-Converting Enzyme Inhibitors; D010795:Phthalic Acids; D004656:Enalapril; C044731:magnesium monoperoxyphthalate