INTRODUCTION:

Telmisartan is 4’-[1,4’-dimethyl-2’-propyl-(2,6’-bi-1H-benzimidazole]-1’-yl)methyl][1,1’-biphenyl]-2-carboxylicacid;4’-[[4-methyl-6-(1-methyl-2-benzimidazolyl)-2-propyl-1-benzimidazolyl]methyl]-2-biphenylcarboxylic acid¹. Telmisartan is a new angiotensin II receptor antagonist for the treatment of essential hypertension usually given in combination with amlodipine. Amlodipine besylate is 3-ethyl-5-methyl (4R-S)-2-[(2-aminoethoxy)-methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3-5-dicarboxylate-benzenesulphonate² and is used as calcium antagonist. Estimation of these drugs by spectrophotometric method has been published by the authors of this paper³. Literature survey of these two drugs revealed that some spectrophotometric, RP-HPLC,

HPTLC methods have been developed for estimation of individual drugs and in combination with other drugs and in plasma^4-19. No method has been developed for the simultaneous estimation of telmisartan and amlodipine in formulations.

EXPERIMENTAL:

Instrumentation: Shimadzu UFLC, UV/Vis detector SPD 20A, LC 20AT Pump system. The Chromatography column used was a reverse phase Phenomenex Gemini C₁₈ column (250x4.60mm, particle size 5µ).

Chromatographic conditions:

The mobile phase consists of mixture of phosphate buffer²⁰ pH 3.0 and acetonitrile in the ratio of 60:40 v/v and was filtered through 0.45 µ membrane filter and sonicated before use. The flow rate of mobile phase was maintained at 1.0 mL/min. The temperature is ambient and the volume of injection was 20µL. The eluent was monitored at 251nm.

Preparation of mixed standard solution:

A mixed standard of telmisartan and amlodipine solution was prepared by mixing aliquot quantities of the stock solutions to yield 160-240µg/mL of telmisartan and 25-45µg/mL of amlodipine with mobile phase.

Preparation of sample solution:

Twenty tablets were accurately weighed and powdered. The powder equivalent to 40mg of telmisartan was accurately weighed and transferred into a 100mL volumetric flask. The contents were dissolved in 25mL of the mobile phase and sonicate for 15min. Then the solution was made up to the volume with the mobile phase. The resulting solution was filtered through a nylon membrane filter and the first 5mL of the filtrate was discarded. Resulting solution was used for analysis.

PROCEDURE:

Evaluation of the drug in Pharmaceutical formulations was successfully analyzed by applying 20µl of filtered final solution to HPLC system to obtain the chromatogram. The content of the drug was calculated by comparing peak area of sample and standard. The method was validated by establishing linearity, accuracy and precision of application.

RESULTS AND DISCUSSION:

The present study was carried out to develop a simple, accurate and precise HPLC method for the analysis of telmisartan and amlodipine in tablet dosage forms. The mobile phase consisting of Phosphate buffer: acetonitrile (60:40) pH 3.0 with flow rate of 1.0ml/min was found to give R_t 4.427min for telmisartan and 2.643min for amlodipine. Statistical parameters such as regression equation, slope (b), intercept (a), correlation co-efficient (r), percent relative standard deviation (% RSD) and standard error (SE) obtained from different concentrations were calculated and the results are summarized in Table 1. To study the accuracy and reproducibility of the proposed methods, recovery experiments were carried out by adding a known amount of drug to pre analyzed sample and the percentage recovery was calculated. The results of assay and recovery are furnished in Table 2. The chromatographic parameters were also validated by system suitability studies^21-22 Table 2. The results indicate that there is no interference of other ingredients present in the formulations. Thus, the proposed method is cost effective, faster, and can be used for routine analysis.

Table 2: System suitability and statistical parameters for and TEL and AML combination by HPLC

S. No.	Parameters	Results obtained
S. No.	Parameters	TEL	AML
1.	No. of theoretical plates	3,882	2,715
2.	Linearity in μg/mL	160-240	25-45
3.	Accuracy (% recovery)	102.4	101.6
4.	LOD (μg/mL)	11.6908	2.3369
5.	LOQ (μg/mL)	35.4267	7.0816
6.	Capacity factor	4.09	2.41
7.	Asymmetry factor	1.10	1.62
8.	Resolution	7.5
9.	Correlation coefficient	0.9995	0.9995
10.	Slope (m)	6.1956	17.7534
11.	Intercept	9.9762	5.7136
12	Relative standard deviation (%)	0.3187	0.2374

TEL- Telmisartan, AML- Amlodipine

REFERENCES:

1. The Merck Index, Merck and Co. Inc., Whitehouse Station, NJ., 14th edition 2006, pp 1569.

2. British Pharmacopoeia 2007, London: The Stationery Office, pp 137.

3. Angayer kanchana S, Aruna A, Niraimathi V, Jerad Suresh A. Simultaneous determination of telmisartan and amlodipine besylate in tablet dosage form by spectrophotometry. International Journal of Chemical Sciences 2010.8(2):1174-1180.

4. Wankhede SB, Tajne MR, Gupta KR, Wadodkar SG. RP-HPLC method for simultaneous estimation of telmisartan and hydrochlorothiazide in tablet dosage form. Indian Journal of Pharmaceutical Sciences 2007. 69(2):298-300.

5. Palled MS, Chatter M, Rajesh PMN, Bhat AR. Difference spectrophotometric determination of telmisartan in tablet dosage forms. Indian Journal of Pharmaceutical Sciences 2006. 68(5):685-686.

6. Bhat L, Godge R, Vora A, Damle M. Validated RP-HPLC method for simultaneous determination of telmisartan and hydrochlorothiazide in pharmaceutical formulation. Journal of liquid chromatography and related technologies 2007. 30(20):3059-3067.

7. Xu M, Song JF, Liang Y. Rapid determination of telmisartan in pharmaceutical preparations and serum by linear sweep polarography. Journal of Pharmaceutical and Biomedical analysis. 2004. 34(3):681-687.

8. Patil K, Rane V, Sangshetti J, Shinde D. A stability-indicating LC Method for the simultaneous determination of telmisartan and ramipril in dosage form. Chromatographia. 2008 67(7-8):575-582.

9. Li P, Wang Y, Wang Y, Tang Y, Fawcett JP, Cui Y, Gu J. Determination of terlmisartan in human plasma by liquid chromatography-tandem mass spectrometry. Journal of Chromatography R 2005. 828*1-2):126-129.

10. Shri BM. Development and validation of a HPTLC method for the simultaneous estimation of telmisartan and hydrochlorothiazide in tablet dosage form. Indian Journal of Pharmaceutical Sciences 2007. 69(2):202-205.

11. RP-HPLC determination of telmisartan in tablet dosage forms. Indian Journal of Pharmaceutical Sciences 2005. 67(1):108-110.

12. Bebawy LI, Abbas SS, Fattah LA, Refaat HH. Application of first derivative, ratio derivative spectrophotometry, TLC-densitometry and spectrofluorimetry for

13. the simultaneous determination of telmisartan and hydrochlorthiazide in pharmaceutical dosage forms and plasma. Il Farmaco 2005.60(10):859-67.

14. Shah DA, Bhatt KK, Shankar MB, Metha RS, Gandhi TR, Baldania SL. RP-HPLC determination of atorvastatin calcium and amlodipine besylate combination in tablets. Indian Journal of Pharmaceutical Sciences 2006.68:796-9.

15. Vora D, Kadav A. Development and validation of simultaneous HPLC method for estimation of bisoprolol fumerate and amlodipine besylate from tablets.Indian Journal of Pharmaceutical Sciences 2008.

16. Mohammadi A, Rezanour N, Dogaheh MA, Bidkorbeh GF, Hashem M, Walker RB. A Stability indicating HPLC assay for the simultaneous determination of atorvastatin and amlodipine in commercial tablets. J Chromatogr B Analyt Technol Biomed Life Science 2007. 846(1-2):215-21.

17. Malesuic MD, Cardoso SG, Bajerski I, Lanzanova FA. Determination of amlodipine in pharmaceutical dosage forms by liquid chromatography and ultraviolet spectrophotometry. Journal of AOAC International 2006. 89(2):359-64.

18. Naidu KR, Kale UN, Shingare MS. Stability indicating RP-HPLC method for simultaneous determination of amlodipine and benazepril hydrochloride from their combination drug product. J Pharm Biomed Anal 2005.1;39(1-2):147-55.

19. Rahman N, Singh M, Hoda MN. Application of oxidants to the spectrophotometric determination of amlodipine besylate in pharmaceutical formulations. Farmaco 2004. 59(11):913-9.

20. Prasad CVN, Saha RN, Parimoo P. Simultaneous determination of amlodipine-enalapril maleate and amlodipine-lisinopril in combined tablet preparations by derivative spectrophotometry. Pharmacy and Pharmacology Communications 1999. 5(6):383-88.

21. Indian Pharmacopoeia, Government of India, The Controller of Publications, New Delhi, 1996. Vol.II.,ppA-144- A-145.

22. Sethi PD. High Performance Liquid Chromatography Quantitative analysis of Pharmaceutical formulations.CBS Publishers and Distributors, New Delhi.pp60-61,173-210.

Received on 31.08.2010 Modified on 04.09.2010

Research J. Pharm. and Tech. 4(3): March 2011; Page 428-429

Tablet	Label claim (mg)	Amount found by proposed method (mg)*	% Label Claim	Amount of drug added	Amount of drug recovered	% recovery
Telmisartan	40.000	40.55	101.37	20	20.48	102.4
Amlodipine	5.000	4.936	98.73	2.5	2.54	101.6