Novel Analytical Method For The Determination Of Atenolol In Pharmaceutical Preparations

: An accurate, and sensitive novel method was designated chemically for the determination of atenolol in pharmaceutical drugs. The complex formation between copper(II) and atenolol was studied both in aqueous and methanolic media. Complex formation depend on reaction conditions at different metal-to-ligand molar ratios. The mononuclear violet complex cation Cu(Atenolol) 4+2 contains two ligands in an anionic bidentate form (through the hydroxyl oxygen and amino nitrogen) and two in a neutral form bound monodentately with an distorted octahedral geometry. The new analatical method based on measuring absorbance in UV-visible at λmax 350nm. Optimum pH and divalent copper ion concentration were estimated. Linearity(40-250), detection limit 07*10 -7 M. were determined. The complex is identified with UV-visible and IR spectra. The molar ratio also investigated and found 1:4(Cu:Atn).

contains two ligands in an anionic bidentate form (through the hydroxyl oxygen and amino nitrogen) and two in a neutral form bound monodentately with an distorted octahedral geometry.The new analatical method based on measuring absorbance in UV-visible at λmax 350nm.Optimum pH and divalent copper ion concentration were estimated.Linearity(40-250), detection limit 07*10 -7 M. were determined.The complex is identified with UV-visible and IR spectra.The molar ratio also investigated and found 1:4(Cu:Atn).

Introduction:
Atenolol is a member of a class of drugs known as beta-blockers (beta adrenergic antagonists) [1][2] .Atenolol designated chemically as (RS)-4-(2hydroxy-3-isopropylaminopropoxy) phenylacetamide, is commercially available as a racemic mixture (rac-atenolol), Atenolol and metoprolol (internal standard).4] Atenolol (Atn) is a β 1selective (cardio selective) β-adrenergic receptor-blocking agent without membrane-stabilizing or intrinsic sympathomimetic (partial agonist) activities.This preferential effect is not absolute however, and, at higher doses, Atn inhibits β 2 -adrenoreceptors, chiefly located in the bronchial and vascular musculature. 5Like other antihypertensive drugs, Atn lowers the systolic and diastolic blood pressure by 15% to 20% in a single drug treatment.In long-term treatment, it has the ability to reduce cardiovascular mortality. 6Atn is also used to treat myocardial infarction (heart attack) and arrhythmias (rhythm disorders), angina (chest pains), and disorders arising from decreased circulation and vascular constriction, including migraine.Atn may be used alone or concomitantly with other antihypertensive agent s including thiazide-type diuretics, hydralazine, prazosin, and α-methyldopa. 7The most serious adverse effects are heart failure, heart block, and bronchospasm.Reactions tend to be more severe after intravenous injection as opposed to oral administration. 8

Standard Solutions:
Stock solution of Atenolol (1000ppm) was prepared in distilled water.Stock solution of Copper (1000ppm) from CuCl 2 .H 2 O was prepared in distilled water.Optimum conditions for the complex 1: Concentration of metal ion: Optimum concentration of the metal ion determined by the additions of 0.2-0.4mL of 1000ppm solution of metal ion to 4mL of 1000ppm Atenolol then extracting the complex after each addition and measuring the absorbance at λmax =350nm (as shown in fig.1).2: pH: Optimum pH for the complex were determined by changing the pHs, of the reaction solution (1-8) by the addition of 0.1N HCl to the solution of metal ion and the drug.The complex is extracted after each addition and measuring the absorbance at λmax =350nm (as shown in fig.2).

Preparation of Standard Curve:
The complex was standardized by the reaction of (0.1-1mL) 1000ppm Atenolol standard solution with 1000ppm (0.5mL) Cuppric chloride standard solution and extracting the complex and measuring the absorbance at λmax =350nm (as shown in fig.5).

Extraction Procedure:
Crash the Atenolol tablets then dissolve in methanol.The filtrate dried and recrystalized from methanol.The complex was synthesized by the reaction of Atenolol solution with copper ion solution, then extraction of complex by methanol and measure the absorbance at λmax, 350nm.

Results and Discussion
The Copper ion react hardly with the ligand in molar ratio 1:4 and 1:1.The molar ratio 1:4 (our target) produce the violet crystal of the complex CuAt 4 in methanolic medium, and the molar ratio 1:1 produce the green crystal of the complex Cu 2 At 2 in aqueous medium.The violet crystal of the complex CuAt 4 is soluble in pH 2.5 and denaturated at pH over 6.
The chemical structure of the ligand (Atenolol) has more than one coordination center because there is hydroxyl, carbonyl, and amino groups.When we compare the IR spectrum of ligand with that of complex we found: 1: The hydroxy band become broader in the complex than that of the ligand that mean there is a bonding between hydroxy group(the oxygen of hydroxy group) and the metal, another evidence for that is the band at 470cm -1 for the coordination of metal with oxygen of hydroxy group , and there is another band at 430cm 2: Changing of carbonyl band from 1700cm -1 (in the ligand) to 1660cm -1 (in the complex) and that may refer to the stability of the carbonyl group.
3: Changing of hydroxyl band from 3400cm -1 (in the ligand) to 3200cm -1 (in the complex) and changing of amino band from 3500cm -1 (for the ligand) to 3400cm -1 (for the complex) and that may be refer to the stability of the hydroxy and amino groups, or that mean these groups are flat with metal.Atenolol react with Cu(II) in methanolic medium in molar ratio M:L 4 at the pH 2 to give violet crystal of the complex (CuAtn 4 ) 2+ .The complex dissolved at the pH 2.5 and decomposed at pH 6.

Figure 5 :
Figure 5: Standard curve or determination of Atenolol in pharmaceutical preparations at λmax =350nm.

9002 05 Optimum conditions for the complex 1: Concentration of metal ion:
Optimum concentration of the metal ion determined as it found form Figure1 (Concentration vs absorbance).The best concentration were given from the highest absorbance,