INTRODUCTION:

Atrovastatin (fig.1a) chemically it is 2-(4-flurorophenyl) β, δ-dihydroxy-5-isopropyl-3-phenyl-4-(phenylamino) carbonyl-1H-Pyrrole-1-heptanoic acid trihydrate calcium salt¹. It is a synthetic lipid lowering agent and an inhibitor of 3-hydroxy-3-methylglutaryl-coenyme A (HMG-CoA) reductase². This enzyme catalyzes the conversion of HMG-CoA to mevalonate, an early and rate limiting stage in cholesterol biosynthesis.

Telmisartan (fig.1b) chemically it is 4’-[[4-methyl-6-(1-methyl-1H-benzodiazol-2-yl)-2-propyl-1H-benzodiazol-1-yl] methyl biphenyl-2-carboxylic acid³. It is acts as a selective modulator of Peroxisome proliferator-activated receptor gamma (PPAR-γ), a central regulator of insulin and glucose metabolism⁴.

(a)

(b)

Fig 1: Chemical structure of Atorvastatin (a); Telmisartan (b)

Literature survey reveals that there are many methods for determination of either ATR or TEL and in combination with other drug in combination dosage forms. None of the reported analytical method describes a simultaneous determination of ATR and TEL in tablet dosage form by UV and HPLC method. Hence it was proposed to attempt the development of simple, accurate, rapid and economic method for simultaneous determination of ATR and TEL in pharmaceutical formulation.

MATERIALS AND METHODS:

Standard Atorvastatin and Telmisartan were provided by Lupin Laboratories, Mumbai. All other chemicals were of analytical grade. Scanning of drugs were done on double beam UV –Spectrophotometer model Shimadzu 1601 with 10 mm matched quartz cells.

Preparation of Standard Drug Solution:

Standard stock solution A: An accurately weighed quantity of ATR (50.0 mg) was dissolved in methanol (25.0 mL) in volumetric flask (50 mL). The volume was made up to mark with methanol. Appropriate dilution were made from this resulting stock solution with methanol so as to get a concentration of 100 µg/mL

Standard stock solution B: An accurately weighed quantity TEL (50.0 mg) was dissolved in methanol (25mL) in volumetric flask (50mL). The volume was made up to mark with methanol. Appropriate dilution were made from this resulting stock solution with methanol so as to get a concentration of 100 µg/mL

Mixed standard stock solution C: An aliquots portion of ATR stock solution and TEL stock solution in the ratio of 1: 2 were mixed volumetric flask (50mL) and volume was adjusted up to mark with methanol.

Procedure for Determine the Sample Wavelength for simultaneous Analysis:

An aliquots portion of standard stock solution of ATR and TEL were appropriately diluted with methanol to get the concentration 10.0 µg/mL and 20.0 µg/mL respectively. The solutions were scanned in range 400 nm to 200 nm against solvent blank. The ATR shows maximum absorbance at 246.20 nm and TEL shows maximum absorbance at 290 nm. The UV absorbance overlain spectrum of drugs are depicted in Fig.2.

Fig 2. Overlain spectra of ATR and TEL

Study of Beer-Lambert’s Law:

The standard solution of ATR and TEL were diluted with methanol to get series of six standard solution having concentration 5, 10, 15, 20, 25 and30 µg/mL respectively. Similarly, mixed standard solution was diluted solution diluted appropriately to get series of concentration ranging from 1 – 10 µg/mL of ATR. The calibrations curves for (A) ATR (B) TEL and (C) Laboratory mixture are depicted in Fig.3. Regression and Optical characteristics of ATOR and CLOP are shown in table no 01. And Results of analysis of laboratory sample are given in table no 2.

Fig 3. Calibrations curves for (A) ATR (B) TEL and (C) Laboratory mixture.

Table 1: Regression and Optical characteristics of ATOR and CLOP

Parameters	Value for ATR	Value for TEL
Beer’s law limit (µg mL)	5-30	5-30
Correlation coefficient(r)	0.9994	0.9996
Regression equation
Slop	0.0232	0.0594
Intercept	0.0035	0.115

Table 2: results of analysis of laboratory sample

Analyte	*% Concentration estimated (Mean ± SD)**	Coefficient of Variance
ATOR	100.35 ±4.39	0.0019
TEL	100.37 ±0.42	0.0018

*Average of five determination; R.S.D., Relative standard Deviation

Twenty tablets were weighed and finely powdered. An accurately weighed quantity of the powder equivalent to 10.0 mg of ATR was taken in volumetric flask (50 mL) and dissolved in about 10.0 ml methanol and sonicated for 15 min. it was further diluted up to mark with methanol The resulting solution was filtered and aliquot portion of the filtrate was further diluted to get final concentration of about 2 µg/mL of ATR. The absorbance of solution was measured at two selected wavelengths against blank. The results of assay of tablet are given in Table 3. and results recovery study are given in table no 4.

Table 3: Results of analysis of tablet sample

Analyte	Label claim (mg/tab)	*% Label claim estimated(Mean± S.D.)**
ATOR	10	100.85
TEL	20	101.37

Table 4: Recovery study

Drug in standard mixture solution (µg ml)		% Recovery ± S.D.*		Coefficient of Variance
ATOR	TEL	ATOR	TEL	ATOR	TEL
1	2	99.24± 1.07	99.92±0.31	0.0114	0.0005
2	4	99.70±0.86	97.15±167	0.0073	0.280
3	6	100.90±0.25	100.91±0.18	0.006	0.003

S.D.* Standard deviation the results of mean of three reading (n=3)

CONCLUSION:

The most striking feature of this method is its simplicity and rapidity, non-requiring- consuming sample preparation such as extraction of solvents, heating, degassing which are needed for HPLC procedure. It is analysis in quality control analysis. The described method gives accurate and precise results for Atorvastatin and Telmisartan in combined solid dosage form.

RESULTS AND DISSUSSION:

The proposed method for simultaneous estimation of ATOR and TEL in combined sample solution was found to be simple, accurate and reproducible. Beer’s law was obeyed in concentration range of 5-30 µg/ml and 5-30 µg/ml for ATR and TEL. Coefficient of variation was found to be 0.9994 and 0.9995 for ATOR and TEL, respectively. The percentage recoveries were found to be in the range of 101.41±1.095 and 100.54±1.003 for ATOR and TEL respectively. Once the equations are determined, analysis requires only the measuring of the absorbance of the sample solution at two wavelengths selected, followed by few simple calculation.

ACKNOWLEDGEMENT:

The authors are grateful to Lupin laboratories for providing standard Atorvastatin and Telmisartan. We are also like to thanks head of the J. L. Chaturvedi College of Pharmacy, Electronic Zone Building MIDC Hingna Road, Nagpur for providing instrumental facility regarding our project work.

REFERENCE:

1. Myrdele, J. O., Catherine, M. K. and Maryann, R. D., In; The Merck index. An Encyclopedia of Chemicals, Drugs and Biologicals. Whitehouse station, N U, USE. 14th Edn., 2006, 143.

2. Gholamreza, B., Mohammadi, B., Kinani, A., J Chromatogr. B, 2005, 41.

3. Torrealdy, N., Gonza, L., Alonso, R. M., J. Pharm. Biomed. Anal., 32, 2003, 847

4. Marria, R. S., Yaritza, C., Alonso, Sabrina, M. R., J. Pharm. Biomed. Anal., 50, 2009, 194.

Received on 30.08.2011 Modified on 04.09.2011

Asian J. Research Chem. 4(11): Nov., 2011; Page 1777-1779