pK(a) determination of angiotensin II receptor antagonists (ARA II) by spectrofluorimetry.

The acid-base equilibrium constants of a new family of antihypertensive drugs, the angiotensin II receptor antagonists (ARA II), Losartan, Irbesartan, Valsartan, Candesartan cilexetil, its metabolite Candesartan M1 and Telmisartan were determined by spectrofluorimetry. Relative fluorescent intensity (I(F,rel))-pH data were treated by graphical (derivatives and curve-fitting) and numerical methods (LETAGROP SPEFO). The resultant pK(a) values at an ionic strength of 0.5 M were (3.15+/-0.07) for Losartan, (4.70+/-0.06) for Irbesartan, (4.90+/-0.09) for Valsartan, (6.0+/-0.1) for Candesartan cilexetil, (3.9+/-0.1) for Candesartan M1, and (4.45+/-0.09) for Telmisartan.

[1]  W. Stenstrom,et al.  Determination of the Dissociation Constants of Phenol and the Hydroxyl Group of Tyrosine by means of Absorption Measurements in the Ultra-violet , 1925 .

[2]  H. Flood,et al.  High-speed Computers as Supplement to Graphical Methods. II. Some Computer Programs for Studies of Complex Formation Equilibria. , 1962 .

[3]  A. Sioufi,et al.  Automated determination of an angiotensin ii receptor antagonist, cgp 48 933, in plasma by high-performance liquid chromatography , 1994 .

[4]  C. J. Drayton,et al.  Comprehensive heterocyclic chemistry : the structure, reactions, synthesis, and uses of heterocyclic compounds , 1984 .

[5]  R. C. Williams,et al.  Comparison of liquid chromatography, capillary electrophoresis and super-critical fluid chromatography in the determination of Losartan Potassium drug substance in Cozaar tablets. , 1996, Journal of pharmaceutical and biomedical analysis.

[6]  M. de Gasparo,et al.  Pharmacokinetics, disposition and biotransformation of [14C]-radiolabelled valsartan in healthy male volunteers after a single oral dose. , 1997, Xenobiotica; the fate of foreign compounds in biological systems.

[7]  J. Lima,et al.  Acid/base properties of beta-blockers and benzodiazepines in sodium dodecyl sulfate micelles. A spectrophotometric and potentiometric study. , 1998, Journal of pharmaceutical sciences.

[8]  D. Farthing.  Simple high-performance liquid chromatographic method for determination of losartan and E-3174 metabolite in human plasma , 1997 .

[9]  G. Schwarzenbach.  The Determination of Stability Constants , 1962 .

[10]  Luis Angel Fernández,et al.  Fluorim: a Computer Program for the Automated Data Collection and Treatment Using Commercial Spectrofluorimeters , 1991, Comput. Chem..

[11]  M. Lo,et al.  An improved method for the simultaneous determination of losartan and its major metabolite, EXP3174, in human plasma and urine by high-performance liquid chromatography with fluorescence detection. , 1997, Journal of pharmaceutical and biomedical analysis.

[12]  A. Fini,et al.  Acidity constants of sparingly water-soluble drugs from potentiometric determinations in aqueous dimethyl sulfoxide. , 1987, Journal of pharmaceutical sciences.

[13]  M. I. Maguregui,et al.  Determination of the pKa values of beta-blockers by automated potentiometric titrations. , 2000, Journal of pharmaceutical and biomedical analysis.

[14]  J. Bauer,et al.  The angiotensin II type 1 receptor antagonists. A new class of antihypertensive drugs. , 1995, Archives of internal medicine.

[15]  Jerry March,et al.  Advanced Organic Chemistry: Reactions, Mechanisms, and Structure , 1977 .

[16]  G. Flesch,et al.  Absolute bioavailability and pharmacokinetics of valsartan, an angiotensin II receptor antagonist, in man , 1997, European Journal of Clinical Pharmacology.

[17]  Joseph Chamberlain,et al.  The Analysis of Drugs in Biological Fluids , 1985 .

[18]  R. Gilbert,et al.  Determination of losartan and its degradates in COZAAR tablets by reversed-phase high-performance thin-layer chromatography. , 1998, Journal of pharmaceutical and biomedical analysis.

[19]  J. Menéndez,et al.  Solvent effects on the fluorescent emission of some new benzimidazole derivatives , 1995 .