Analytical Study of Some Cardiovascular Drugs

Abstract

This thesis includes seven parts: Part I: Introduction: This part involves a general introduction on the pharmacological background and classification of cardiovascular drugs. Part II: Literature Review: This part includes the structure, physiochemical characters, and different reported methods for the analysis of the studied drugs. Part III: Stability Studies of the Cited Drugs: This part includes explanation of all the stress and forced degradation studies done through the thesis for the studied drugs. Also it includes the different techniques used for the structure elucidation of the degradation products. Part IV: Determination of the Studied Drugs by LC-MS/MS Methods: Section A: Determination of Benazepril and Amlodipine in Pharmaceutical Formulation and with Benazeprilat in Human Plasma by LC-MS/MS Method: This part involves Tandem mass spectrometric determination of the studied drugs in pharmaceutical formulation and in plasma. The mass spectrum of positively charged amlodipine, benazepril and benazeprilat (BENZT) (m/z 409.2), (m/z 425.2) and (m/z 397.0) showed the formation of most intense product ion peak at m/z 238.2, m/z 351.2 and at m/z 351, respectively. Similarly, the mass spectrum of positively charged internal standard (IS) (moexipril, m/z 499.4) showed the formation of most intense product ion peak at m/z 234.2. So, the most intense ion peak for each analyte was chosen for 3 the determination of each analyte in the MRM mode. Retention times for Benazepril, Benazeprilat, Amlodipine, and Moexipril (IS) under the specified conditions were found to be 1.4, 0.6, 1.9, and 1.1 min. respectively. The proposed method was successfully applied for the analysis of the pharmaceutical formulation, and the validity of the method was further assessed by applying the standard addition technique, whereby satisfactory recoveries of authentic added were obtained. The results obtained by the proposed method were statistically compared with those obtained by applying the reference method (1). The calculated t and F values were less than the tabulated ones which reveals that there is no significant difference between the two methods with respect to accuracy and precision. Section B: Determination of Moexipril in Pharmaceutical Formulation and with Moexiprilat in Human Plasma by LC-MS/MS Method: The mass spectrum of positively charged Moexipril and Moexiprilate (MOXT) (m/z 499.4) and (m/z 471) showed the formation of most intense product ion peak at m/z 234.2 and m/z 206, respectively. Similarly, the mass spectrum of positively charged IS (Benazepril, m/z 425.2) showed the formation of most intense product ion peak at m/z 351.2. Retention times for Moexipril, Moexiprilat, and Benazepril (IS) under the specified conditions were found to be 1.1, 0.6, and 1.4 min. respectively. The proposed method was successfully applied for the analysis of the pharmaceutical formulation, and the validity of the method was further assessed by applying the standard addition technique, whereby satisfactory recoveries of authentic added were obtained.