Quantitation of a new potent angiotensin II receptor antagonist, TCV-116, and its metabolites in human serum and urine.
ABSTRACT A sensitive high-performance liquid chromatographic (HPLC) method is described for the determination of a new potent antihypertensive agent, TCV-116, and its two metabolites (M-I and M-II) in human serum or urine. After pre-treatment of the specimens, the analytes were determined using a column switching technique, except for the metabolites in urine which were determined by gradient elution mode HPLC. The quantitation limits for TCV-116, M-I and M-II were all 0.5 ng/ml in serum, and 0.5, 10 and 110 ng/ml in urine, respectively. The methods were applied to clinical trials of TCV-116.
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ABSTRACT: The renin-angiotensin system has an important function in the regulation of blood pressure as well as in pathophysiological processes in the central nervous system. We examined the effects of the angiotensin receptor blocker candesartan (10 mg kg(-1) per day, p.o.) on brain angiotensin II levels in angiotensin II-infused hypertensive rats. Angiotensin II or vehicle was infused subcutaneously for 14 days in Sprague-Dawley rats. Angiotensin II infusion resulted in increased blood pressure, an effect that was blocked by candesartan treatment. There was no effect of the angiotensin II infusion on Angiotensin II levels in the brain or on blood-brain barrier permeability. Brain tissue angiotensinogen and angiotensin converting enzyme mRNA levels were not changed by angiotensin II infusion but were decreased by candesartan treatment. At 2 weeks of treatment, CV11974, an active form of candesartan, was detectable in the plasma but was not detectable in brain tissue. These data suggest that treatment with candesartan decreases brain angiotensin II by decreasing brain angiotensinogen and angiotensin converting enzyme gene expression.Hypertension Research 11/2009; 33(2):161-4. · 2.79 Impact Factor
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ABSTRACT: This article describes the development of flow injection methods for the determination of Candesartan Cilexetil using spectrophotometery and spectrofluorimetry in pharmaceutical formulations. The first method is based on the UV absorption at 270 nm in phosphate buffer containing cetyl trimethylammonium bromide (CTAB) and methanol at pH 6.5. The second method based on the fluorescence excitation and emission at 260 and 384 nm respectively, in phosphate buffer containing sodium dodecyl sulphate (SDS) and methanol at pH 4.0. Calibration graphs were linear over the concentration range of 0.1 to 4.0 μg/ml for UV-method and 0.03 to 2.0 μg/ml for fluorescence method. The limits of detection (3 s) of 0.01 μg/ml for both methods with sample throughput of 80 and 100/h were obtained respectively. The relative standard deviations of 1.2 to 3.2% (n = 4) for UV-method and 0.5 to 1.8% for fluorescence method were achieved in the concentration range studied. The developed methods were applied to pharmaceuticals and the results obtained were compared with HPLC reference method and no significant difference between these methods was observed at 95% confidence level. © 2011 Academic Journals.Scientific research and essays 01/2011; 6(29):6203-6208. · 0.32 Impact Factor
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ABSTRACT: A high-performance liquid chromatographic method with photometric detection has been developed for the determination of five angiotensin II receptor antagonists (ARA II): Losartan, Irbesartan, Valsartan, and Candesartan cilexetil and its metabolite Candesartan M1. Reversedphase chromatography was performed at room temperature on a μBondapak C18 column; compounds were separated by gradient elution with mixtures of acetonitrile and 0.1 M acetate buffer, pH 4, at different flow rates. Detection was at 254 nm. Urine samples were purified by solid-phase extraction on C8 cartridges, a procedure enabling recoveries > 85% for all the drugs except Candesartan cilexetil (71%). The analysis time was less than 50 min, including extraction (chromatographic analysis lasted 25 min). Intra- and inter-day coefficients of variation for all the compounds were below 8% and the method was highly accurate (relative error,RE, usually ca 3%). The accuracy, precision, and sensitivity (limit of quantitation 0.4 μg mL−1) of the method were sufficient for application to the screening of these ARA II in spiked urine samples.Chromatographia 04/2012; 52(11):735-740. · 1.44 Impact Factor