Characterization of major degradation products of an adenosine A2A receptor antagonist under stressed conditions by LC-MS and FT tandem MS analysis.
Parkinson's disease (PD) is a very serious neurological disorder, and current methods of treatment fail to achieve long-term control. SCH 420814 is a potent, selective and orally active adenosine A(2A) receptor antagonist discovered by Schering-Plough. Stability testing provides evidence of the quality of a bulk drug when exposed to the influence of environmental factors. Understanding the drug degradation profiles is critical to the safety and potency assessment of the drug candidate for clinical trials. As a result, identification of degradation products has taken an important role in drug development process. In this study, a rapid and sensitive method was developed for the structural determination of the degradation products of SCH 420814 formed under different forced conditions. The study utilizes a combination of liquid chromatography-tandem-mass spectrometry (LC-MS/MS) and Fourier Transform (FT) MS techniques to obtain complementary information for structure elucidation of the unknowns. This combination approach has significant impact on degradation product identification. A total of ten degradation products of SCH 420814 were characterized using the developed method.
Zhang
Li-Kang
LK
Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. li-kang.zhang@spcorp.com
Pramanik
Birendra N
BN
D058917:Adenosine A2 Receptor Antagonists; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D005583:Fourier Analysis; D006801:Humans; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010300:Parkinson Disease / Q000188:drug therapy; D011743:Pyrimidines / Q000737:chemistry*; D013607:Tablets / Q000737:chemistry; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014230:Triazoles / Q000737:chemistry*
D058917:Adenosine A2 Receptor Antagonists; D011743:Pyrimidines; D013607:Tablets; D014230:Triazoles; C539997:2-(2-furanyl)-7-(2-(4-(4-(2-methoxyethoxy)phenyl)-1-piperazinyl)ethyl)-7H-pyrazolo(4,3-e)(1,2,4)triazolo(1,5-c)pyrimidine-5-amine