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.
- SourceAvailable from: Naohisa Hosomi[show abstract] [hide abstract]
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
- [show abstract] [hide abstract]
ABSTRACT: In this work, an SPE-HPLC method coupled to photodiode array detection was validated in human urine matrix, in order to monitor four antihypertensive angiotensin II receptor antagonist drugs in patients under cardiovascular treatment. For that purpose, experimental design was used. Quantitation was accomplished by the internal standard method. The obtained LOQs were 95, 113, 125, and 85 ng/mL for eprosartan, telmisartan, irbesartan, and valsartan, respectively. The intraday and interday precision and accuracy at four concentration levels in the working range (LOQ-15 microg/mL) were always lower than 11% RSD and 8% relative error. The urine samples proved to be stable during 4 h at room temperature, after three thaw-freeze cycles, and for 2 months at -20 degrees C. No interferences from other endogenous compounds or co-administered drugs were found. The method has been successfully applied to monitor the renal elimination of eprosartan and valsartan during 24 h.Journal of Separation Science 04/2008; 31(4):667-76. · 2.59 Impact Factor
- [show abstract] [hide abstract]
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