title: Polypill for the treatment of cardiovascular diseases part 2. LC-MS/TOF characterization of interaction/degradation products of atenolol/lisinopril and aspirin, and mechanisms of formation thereof.
abstract: A polypill for cardiovascular diseases (CVD) is under development. It is proposed to contain a combination of antithrombotic agent (aspirin), low-dose blood pressure lowering agents, i.e., angiotensin-converting enzyme inhibitor (lisinopril), one among a beta-blocker (atenolol) or diuretic (hydrochlorothiazide), and a statin (simvastatin/atorvastatin/pravatsatin, etc.). Due to the presence of multiple drugs in the same formulation, there is a strong likelihood of interaction among the drugs and/or their products. In a previous study, we observed formation of a number of interaction/degradation products from atenolol and lisinopril in the presence of aspirin. Accordingly, the purpose of this study was to characterize the resolved products using high resolution mass spectrometric and fragmentation analyses using a LC-MS/TOF system. Initially, studies were carried out on the drugs (atenolol, lisinopril and aspirin) to establish their complete fragmentation pattern. These studies were then extended to degraded samples to postulate the structures of interaction/degradation products. The characterized structures were justified through mechanistic explanations.
authors.affiliation: Department of Pharmaceutical Analysis, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S.A.S. Nagar 160062, Punjab, India.
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
authors.forename: Satish
authors.initials: S
authors.lastname: Malik
authors.forename: Saranjit
authors.initials: S
authors.lastname: Singh
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000032:analysis; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000032:analysis; D001241:Aspirin / Q000032:analysis / Q000737:chemistry; D001262:Atenolol / Q000032:analysis / Q000737:chemistry; D002317:Cardiovascular Agents / Q000032:analysis* / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods*; D004338:Drug Combinations; D004347:Drug Interactions; D017706:Lisinopril / Q000032:analysis / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods*; D015394:Molecular Structure; D008970:Molecular Weight; D010975:Platelet Aggregation Inhibitors / Q000032:analysis
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002317:Cardiovascular Agents; D004338:Drug Combinations; D010975:Platelet Aggregation Inhibitors; D001262:Atenolol; D017706:Lisinopril; D001241:Aspirin