Characterization of degradation products of amorphous and polymorphic forms of clopidogrel bisulphate under solid state stress conditions.
The present study deals with the stress degradation studies on amorphous and polymorphic forms of clopidogrel bisulphate. The objective was to characterize the degradation products and postulate mechanism of decomposition of the drug under solid state stress conditions. For that, amorphous form, polymorph I and polymorph II of the drug were exposed to 40 degrees C/75% relative humidity (RH), with and without stressors for 3 months. The samples were analyzed by HPLC, and the relative extent of degradation as well as nature of decomposition was compared among three solid forms. In total, eight degradation products were observed under various stress conditions. The structures of all of them were elucidated using LC-MS/TOF and LC-MS(n) studies. While one matched the known hydrolytic decomposition product of the drug in solution, seven others were new. The postulated degradation pathway and mechanism of decomposition are discussed.
Raijada
Dhara K
DK
Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar, Mohali 160062, Punjab, India.
Prasad
Bhagwat
B
Paudel
Amrit
A
Shah
Ravi P
RP
Singh
Saranjit
S
D002851:Chromatography, High Pressure Liquid / Q000379:methods; D002853:Chromatography, Liquid / Q000379:methods; D000077144:Clopidogrel; D003198:Computer Simulation; D004304:Dosage Forms; D004355:Drug Stability; D006358:Hot Temperature; D006863:Hydrogen-Ion Concentration; D006868:Hydrolysis; D008027:Light; D013058:Mass Spectrometry / Q000379:methods; D015394:Molecular Structure; D010084:Oxidation-Reduction; D010782:Photolysis / Q000528:radiation effects; D010975:Platelet Aggregation Inhibitors / Q000032:analysis / Q000737:chemistry*; D015203:Reproducibility of Results; D013678:Technology, Pharmaceutical; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000032:analysis / Q000737:chemistry; D013997:Time Factors; D014961:X-Ray Diffraction / Q000379:methods
D004304:Dosage Forms; D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine