Identification of the degradation product of ezlopitant, a non-peptidic substance P antagonist receptor, by hydrogen deuterium exchange, electrospray ionization tandem mass spectrometry (ESI/MS/MS) and nuclear magnetic resonance (NMR) spectroscopy.
The degradation product of ezlopitant was isolated from low specific activity material and identified by solution phase hydrogen/deuterium (H/D) exchange and electrospray ionization tandem mass spectrometry (ESI/MS/MS) to be an isopropyl peroxide analog of ezlopitant. The structure of the degradant was further confirmed by nuclear magnetic resonance (NMR) spectroscopy utilizing complete 1H and 13C assignments. Studies were also performed to identify the factors responsible for the oxidative degradation of ezlopitant, which included salt form, storage conditions and salt formation solvent. Of all the variable studies over a 3 weeks period, only a change in the salt form prevented this oxidative degradation.
Kamel
Amin M
AM
Department of Pharmacokinetics, Dynamics and Drug Metabolism, Pfizer Global Research and Development, Eastern Point Road, Groton, CT 06340, USA. amin_m_kamel@groton.pfizer.com
Zandi
Kathleen S
KS
Massefski
Walter W
WW
D001596:Benzylamines / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D003903:Deuterium; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D011522:Protons; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013373:Substance P / Q000037:antagonists & inhibitors*
D001596:Benzylamines; D019086:Bridged Bicyclo Compounds, Heterocyclic; D011522:Protons; D013373:Substance P; C413864:ezlopitant; D003903:Deuterium