Article

Quantitation of a new potent angiotensin II receptor antagonist, TCV-116, and its metabolites in human serum and urine.

Drug Analysis and Pharmacokinetics Research Laboratories, Takeda Chemical Industries, Ltd., Osaka, Japan.
Journal of chromatography. B, Biomedical applications 03/1996; 677(1):123-32. DOI: 10.1016/0378-4347(95)00405-X
Source: PubMed

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.

0 Bookmarks
 · 
112 Views
  • [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. · 1.37 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The addition of polysorbate 20 (T20) is required to achieve "sink" conditions during a dissolution test for tablets with candesartan cilexetil (CC). Polysorbate 20 (0.35%-0.7% w/w) added to 0.05 mol/L of phosphate buffer pH 6.5 dramatically increased the apparent solubility of the drug from 0.8 μg/ml even to 353 μg/ml, while its effect in lower pH or in water was much smaller (20 μg/ml in pH 4.5). The increased concentration of phosphate salts (0.2 mol/l) at pH 6.5 in the presence of 0.7% of polysorbate 20, resulted in further increase of candesartan cilexetil solubility to 620 μg/ml. The change of pH from 1.2 to 7.4 resulted in a 1.5-fold increase of the activation energy and, depending on temperature, 8-14-fold decrease of the degradation rate. When polysorbate 20 increased the activation energy 2-fold, independent of pH, it protected candesartan cilexetil from degradation; however, this effect was temperature dependent and was very small at 310 K-the degradation rate in pH 6.5 decreased by 13% only. It was calculated that in the phosphate buffer pH 6.5 with polysorbate, one can expect during 24 h the degradation at the level of 9.3%, thus a flow-through dissolution apparatus was recommended for testing prolonged release dosage forms.
    AAPS PharmSciTech 05/2014; · 1.78 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    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