INTRODUCTION:

Nadolol chemicaly is 5-[3 [(1, 1 dimethylethyl) amino]-2-hydroxylpropoxyl]-1,2,3,4-naphthalene diol¹, is a long acting antagonist with equal affinity for both β₁ and β₂-adrenergic receptors. It is devoid of both membrane-stabilising and intrinsic sympathomimetic activity, with distinguishing characteristics of relatively long half-life compared to other adrenoceptor antagonists².

Nadolol is used in the management of hypertension, angina pectoris, cardiac arrhythmias, hyperthyroidism and migraine. Like other β-adrenergic blockers, however, it causes a mild increase in plasma volume and antagonizes the thyroxin-mediated stimulation of β-adrenergic receptors. Nadolol is marketed as tablets containing Nadolol alone or in combination with bendroflumethiazide. This drug is official in BP³ and USP⁴. According to literature survey HPLC^5-13, Colorimetry^14-15, Fluorimetry¹⁶, GLC¹⁷andSpectrophotometric¹⁸, methods have been developed for the determination of Nadolol. The aim of the present work was to develop a simple, validated, and rapid visible spetrophotometric method for routine analysis of Nadolol in pure drug and dosage form. The chemical structure of Nadolol was reported in fig-1.

EXPERIMENTAL:

INSTRUMENT:

All spectral and absorbance measurements were made on an ELICO-SL164 UV /VIS double beam spectrophotometer with 10mm matched quartz cells.

REAGENTS:

All the reagents used were of analytical grade and the solutions were freshly prepared. The reagents used in this method are Sodium nitroprusside (SNP 5%), Hydroxylamine Hydrochloride (NH₂OH Hcl 5%), Sodium Carbonate (Na₂CO₃10%).

PROCEDURE:

Standard stock solution:

A standard solution containing 1 mg/ml was prepared by dissolving 50 mg of Nadolol and diluted to 50 ml with distilled water.

Method:

In to a series of 10 ml volumetric flasks, 0.1-0.5 ml (1 mg/ml) of working standard solution ,1 ml of SNP and 2 ml of hydroxyl amine solution were successively added to each flask and shaken for 5 min, then 1ml of sodium carbonate was added and shaken for 20-25 min. Then contents were diluted to 10ml with distilled water and the absorbance measured after 10 min at 440 nm against reagent blank. The amount of Nadolol present was computed and its calibration graph was reported in fig-2.

Fig-1 Chemical structure of Nadolol

Fig-2 Beer^’s law plot of Nadolol

Preparation of sample solution:

Twenty tablets of commercial samples of Nadolol were accurately weighed and powdered. Tablet powder equivalent to 50 mg of Nadolol was dissolved in water and made up to 50 ml with distilled water; the solution was filtered and analyzed as given under the assay procedure for bulk samples. Results were represented in Table 1. None of the excipients usually employed in the formulation of tablets interfered in the analysis of Nadolol by the proposed method.

RESULTS AND DISCUSSION:

Validation of the method:

The optimum conditions for the color development was established by varying the concentration and order of addition of SNP, NH₂OH,HCl and Na₂CO₃ and observing the effect produced on the absorbance of the colored species

The optical characteristics such as Beer^’s law limits, molar absorptivity and sandell^’s sensitivity were given in Table-1. The precision of the method was found by measuring the absorbance of 6 separate samples containing known amounts of drugs and the results obtained are incorporated in Table-1. Regression analysis using the method of least squares was made to evaluate the slope (b), intercept (a) and correlation coefficient (r).

The accuracy of the method was ascertained by comparing the results by proposed results of studied methods and those of reference. The similarity of the results is obvious evidence that during the application of these methods the excipients present in the formulation do not interfere in the assay of proposed method. As an additional check of accuracy of the proposed method recovery studies were carried out. The recovery of the added amounts of standard drug was studied at 3 different levels. Each level was repeated 6 times. From the amount of drug found, the percentage recovery was calculated and depicted in Table-2.

Table-1: Optical and Regression characteristics of the proposed method for Nadolol

Parameters
λmax,nm	440
Beer^’s law Limit(mg/ml)	0.1-0.3
Molar absorptivity,L/mol.cm	1.9983x10⁴
Sandell^,s sensitivity (µg/cm²/0.001Absorbance unit)	0.2
Regression equation Y=a+bc Slope(b) Intercept(a)	0.002522 0.7486
Correlation coefficient	0.998607

Table -2: Analysis of Tablet formulation

Label claim

Amount found

%R.S.D

%Recovery

[n=5]

39.9

0.8581

99.75

79.7

0.7581

99.62

CONCLUSION:

The proposed visible Spectrophotometric method is simple, sensitive and accurate with reasonable precision, accuracy and constitute better alternative to the existing ones for the routine determination of Nadolol in bulk and pharmaceutical formulations.

REFERENCES:

1. Merck Index. Merck Research laboratories. 1996; 12^th edition: 1089.

2. Hoffman BB. In Goodman and Gilman’s. The Pharmacological Basis of Therapeutics, Edited by Hardman JG and Limbard LE. McGraw-Hill, New York. 2001; 10^th edition: 254.

3. British Pharmacopoeia. 2002; Volume-1: 1189.

4. US Pharmacopoeia (XXIV) and National formulary (XIX). Asian Edn., US Pharmacopoeial Convention, USA. 2000; 1134.

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Received on 22.06.2010 Modified on 02.07.2010

Asian J. Research Chem. 3(4): Oct. - Dec. 2010; Page 1038-1040