Abstract
Abstract Five various chemometric methods were established for the simultaneous determination of azilsartan medoxomil (AZM) and chlorthalidone in the presence of azilsartan which is the core impurity of AZM. The full spectrum-based chemometric techniques, namely partial least squares (PLS), principal component regression, and artificial neural networks (ANN), were among the applied methods. Besides, the ANN and PLS were the other two methods that were extended by genetic algorithm procedure (GA-PLS and GA-ANN) as a wavelength selection procedure. The models were developed by applying a multilevel multifactor experimental design. The predictive power of the suggested models was evaluated through a validation set containing nine mixtures with different ratios of the three analytes. For the analysis of Edarbyclor® tablets, all the proposed procedures were applied and the best results were achieved in the case of ANN, GA-ANN, and GA-PLS methods. The findings of the three methods were revealed as the quantitative tool for the analysis of the three components without any intrusion from the co-formulated excipient and without prior separation procedures. Moreover, the GA impact on strengthening the predictive power of ANN- and PLS-based models was also highlighted.
Highlights
Metabolic activation of a drug leading to reactive metabolite(s) that can covalently modify proteins is considered an initial step that may lead to drug-induced organ toxicities.Chemically, azilsartan medoxomil (AZM) is known as ((5-methyl-2-oxo-1,3-dioxol-4yl) methyl 2-ethoxy-1-((2′(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl) biphenyl-4-yl) methyl)-1H-benzimidazole-7-carboxylate) (Figure 1)
The powder corresponding to 12.5 mg of CHT and 40 mg of AZM was carefully transferred into a 20 mL volumetric flask containing 10 mL methanol
The solution mixture was extracted through sonication, and partial least squares (PLS) and PCR models were chosen because they are fullspectrum chemometric procedures
Summary
Azilsartan medoxomil (AZM) is known as ((5-methyl-2-oxo-1,3-dioxol-4yl) methyl 2-ethoxy-1-((2′(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl) biphenyl-4-yl) methyl)-1H-benzimidazole-7-carboxylate) (Figure 1). Azilsartan (AZ), the active metabolite and the main degradation product of AZM, is a novel nonpeptide angiotensin II type 1 (AT1) receptor blocker (ARB) that was lately approved for hypertension treatment [1]. It has a superior capacity to regulate systolic blood pressure compared to other commonly used ARBs. Better antihypertensive effects of AZ may be due in part to its exceptionally strong and consistent ability to inhibit the binding of angiotensin II to AT1 receptors [2]. Chlorthalidone (CHT) is chemically (RS)-2-chloro-5(1-hydroxy-3oxoisoindolin-l-yl)benzenesulphonamide (Figure 1). It is a diuretic drug used to treat hypertension [3]. US Food and Drug Administration (US-FDA) had approved Edarbyclor® that contains AZM and CHT for
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