1. INTRODUCTION:
Telmisartan, a nonpeptide molecule, is chemically described as 4'-[(1, 4’-dimethyl-2'-propyl [2, 6’-bi-1H-benzimidazol]-1'-yl) methyl]-[1, 1’-biphenyl] -2-carboxylic acid. Its empirical formula is C33H30N4O2, its molecular weight is 514.63.1
Telmisartan, an orally active angiotensin II antagonist acting on the AT1 receptor subtype.2 Telmisartan is used for the treatment of hypertension (high blood pressure). It also is used for reducing the risk of heart attack, stroke, or death from cardiovascular causes in patients 55 years of age or older at high risk of developing major cardiovascular events who are unable to take ACE inhibitors.3
Recent studies suggest that Telmisartan may also have PPAR-gamma agonistic properties that could potentially confer beneficial metabolic effects.4 Micardis (Telmisartan) is in a group of drugs called angiotensin II receptor antagonists. It works by decreasing certain chemicals in the body that cause blood vessels to constrict and sodium and fluid to be stored by the kidneys.5-7
Literature survey reveals that several methods like Spectrophotometry8-9, HPLC10-13, HPTLC and LC-MS14-15 were reported for the determination of Telmisartan in combination with other drugs as well as in biological fluids. These methods are too expensive and time consuming. An attempt has been made to develop a simple, economical, precise, accurate and reproducible spectrophotometric method for estimation of Telmisartan in bulk as well as pharmaceutical formulations (Fig.1).
2. EXPERIMENTAL:
2.1. Instrumentation:
Spectral runs were made on a Shimadzu UV-Visible spectrophotometer, model- 1800 (Japan) was employed with spectral bandwidth of 1 nm and wavelength accuracy of ± 0.3 nm with automatic wavelength corrections with a pair of 10 mm quartz cells.
2.2. Materials and reagents:
All the reagents used in this assay were of analytical grade, pure Telmisartan was obtained from LUPIN LTD Pune India. The commercial fixed dose tablet formulations MICARDIS containing 40 mg Telmisartan were procured from the local market and methanol used analytical grade from Loba Chemicals, Mumbai.
2.3. Standard stock solutions:
Standard Stock solutions of Telmisartan were prepared by accurately weigh and dissolving 10 mg of Telmisartan in 100 ml methanol to get concentration of 100μg/ml which is the standard stock solution.
Figure 1: Chemical structure of Telmisartan
2.4. Working standard solution:
From the above stock solution, 0.2ml was pippetted into a 10ml volumetric flask and the volume was made up to the mark with methanol to prepare a concentration of 2μg/ml. Then the sample was scanned in UV-VIS Spectrophotometer in the range 400-200nm using methanol as a blank and the Wavelength corresponding to maximum absorbance (λmax) was found to be 297nm (Fig.2)
Figure 2: Zero order spectra of telmisartan
2.5. Calibration Curve:
0.2ml of the 100μg/ml solution was diluted to 10ml by using methanol to produce 2μg/ml solution. 0.4ml, 0.6ml up to 2.2ml of 100μg/ml solution was diluted to 10ml using methanol to produce 4μg/ml, 6μg/ml and 22μg/ml solutions respectively. A calibration curve for ibuprofen was plotted. Statistical parameters like the slope, intercept, coefficient of correlation, standard deviation, relative standard deviation, and standard error were determined.
2.6 Analysis of Marketed Tablet Formulation:
Twenty tablets were weighed and finely powdered. A portion of the powder equivalent to about 10mg of Telmisartan was weighed accurately, dissolved and diluted to 100 ml with methanol. The sample solution was filtered using Whatmann filter paper. Further dilution was carried out with methanol. The general procedures for described under calibration were followed and the concentrations of Telmisartan were calculated at 297nm.
3. VALIDATION:
The methods were validated with respect to accuracy, linearity, limit of detection (LOD) and limit of quantitation (LOQ) (Table no.1).
Table No.1: Optical characteristics and Other Parameters
|
Sr. No. |
Parameters |
Observation |
|
1. |
λmax (nm) / wavelength range (nm) |
297 |
|
2. |
Beer’s-Lambert’s range (μg/ml) |
2-22 |
|
3. |
Coefficient of Correlation |
0.99992 |
|
4. |
Slope |
0.050275 |
|
5. |
Y – Intercept |
0.01659 |
|
6. |
Sandell’s Sensitivity (mg/cm2/0.001 absorbance unit) |
0.019891 |
|
7. |
Molar absorptivity |
25872.811554 |
|
8. |
LOD (μg/ml) |
0.03787 |
|
9. |
LOQ (μg/ml) |
0.11477 |
3.1. Accuracy (recovery test):
The accuracy of the method was determined by preparing solutions of different concentrations that is 80%, 100% and 120% in which the amount of marketed formulation (MICARDIS-40mg) was kept constant (10mg) and the amount of pure drug was varied that is 8mg, 10mg and 12mg for 80%, 100% and 120% respectively. The solutions were prepared in triplicates and the accuracy was indicated by % recovery (Table no.2).
Table No.2: Result of Analysis of Telmisartan in marketed tablet formulation
|
Tablet |
Label Claim (mg) |
Estimated* (mg) |
% Estimated* |
% Recovesry * |
|
Micardis |
40 |
39.70 |
99.2568 |
99.45 |
Where, * indicates mean of six determinations.
3.2. Linearity:
The linearity of measurement was evaluated by analysing different concentration of the standard solution of telmisartan. Beer-Lambert’s concentration range was found to be 2-22 μg/ml
3.3. Limit of detection (LOD) and limit of quantitation (LOQ):
The LOD and LOQ of Telmisartan were determined by using standard deviation of the response and slope approach as defined in International Conference on Harmonization (ICH) guidelines.
4. RESULTS AND DISCUSSION:
The methods discussed in the present work provide a convenient and accurate way for analysis of Telmisartan in its pharmaceutical dosage form. Absorbance maxima of Telmisartan at 297 nm were selected for the analysis. Linearity for detector response was observed in the concentration range of 2-22 μg/ml. Percentage label claim for Telmisartan in tablet analysis, was found close to 100 %. Standard deviation for six determinations of tablet sample was found to be less than ±2.0 indicating the precision of the methods. Accuracy of proposed methods was ascertained by recovery studies and it was found in the range of close to 100% and values of standard deviation was satisfactorily low indicating the accuracy of all the methods(Table no.3).
Table No.3: Results of statistical analysis
|
Tablet |
Label Claim (mg) |
S.D.* (±) |
% R.S.D.* |
S.E.* |
|
Micardis |
40 |
0.198914 |
0.200403 |
0.114843 |
Where, * indicates mean of six determinations.
5. CONCLUSIONS:
The developed method was found to be simple, sensitive, accurate, precise, reproducible, and can be used for routine quality control analysis of Telmisartan in bulk and pharmaceutical formulation.
6. ACKNOWLEDGEMENTS:
Authors are grateful to LUPIN LTD Pune India, for providing the gift sample of Telmisartan. We are also thankful to the Principal, Government College of Pharmacy, Karad for providing the necessary facilities to carry out this research.
7. REFERENCES:
1. The Merck Index, 13th Ed., Merck and Co.Inc.,White House Station, NJ; 2001. p.1628.
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3. Karlberg BE, Lins LE, Hermansson K. Efficacy and safety of telmisartan, a selective AT1 receptor antagonist, compared with enalapril in elderly patients with primary hypertension. TEES Study Group. J Hypertens. 1999 Feb; 17(2):293-302.
4. Balt JC, Mathy MJ, Nap A, Pfaffendorf M, van Zwieten PA. Effect of the AT1- receptor antagonists losartan, irbesartan, and telmisartan on angiotensin II-induced facilitation of sympathetic neurotransmission in the rat mesenteric artery. J Cardiovasc Pharmacol. 2001 Jul; 38(1):141-148.
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Received on 23.04.2011 Modified on 14.05.2011
Accepted on 09.06.2011 © AJRC All right reserved
Asian J. Research Chem. 4(11): Nov., 2011; Page 1664-1665