Development of a novel 96-microwell assay with high throughput for determination of olmesartan medoxomil in its tablets

Olmesartan medoxomil (OLM); (5-methyl-2-oxo-2H-1,3-dioxol-4-yl)methyl 4-(2-hydroxy-propan-2-yl)-2-propyl-1-({4-[2-(2H-1,2,3,4-tetrazol-5-yl)phenyl]phenyl}methyl)-1H-imidazole-5-carboxylate (Figure 1), is the newest member of non-peptide angiotensin II receptor antagonists used worldwide in the treatment of hypertension. It is an ester prodrug, which is completely and rapidly hydrolyzed to the active acid form, olmesartan. OLM exerts its action mainly via a selective blockade action on AT1 receptors and the consequent reduced pressor effect of angiotensin II [1,2]. OLM may be used alone or in combination with other antihypertensive agents. The FDA has determined that the benefits of OLM continue to outweigh its potential risks when used for the treatment of patients with high blood pressure according to the drug label. OLM is also used by some people who are treated with an unproven therapy for autoimmune diseases known as the Marshall Protocol.OLM has not yet been officially described in any pharmacopoeia. A literature survey revealed that several analytical methods were reported for its determination. These methods include high-performance thin-layer chromatography [3], liquid chromatography [3-9], and capillary zone electrophoresis [10]. These methods were not simple to perform, time-consuming, and utilize expensive instruments that are not available in most quality control laboratories. In general, spectrophotometry is the most widely used technique in pharmaceutical analysis because of its inherent simplicity and wide availability in most quality control laboratories [11]. However, few spectrophotometric methods have been reported for the analysis of OLM in its pharmaceutical tablets [12-15]. Unfortunately, these methods suffer from major drawbacks such as decreased selectivity due to measuring the native light absorption of OLM in the blue-shifted ultraviolet region, which might be subjected to interferences [12-14]. Besides the tedious liquid-liquid extraction