Get 20M+ Full-Text Papers For Less Than $1.50/day. Subscribe now for You or Your Team.

Learn More →

Absorbance correction method for estimation of telmisartan and metoprolol succinate in combined tablet dosage forms

Absorbance correction method for estimation of telmisartan and metoprolol succinate in combined... Original Article Absorbance correction method for estimation of telmisartan and metoprolol succinate in combined tablet dosage forms Aim and Background: The present manuscript describes simple, sensitive, rapid, accurate, precise and economical spectrophotometric method for the simultaneous determination of telmisartan and metoprolol succinate in combined tablet dosage form. Materials and Methods: The method is based on the absorbance correction equations for analysis of both the drugs using methanol as solvent. Telmisartan has absorbance maxima at 296 nm and metoprolol succinate has absorbance maxima at 223 nm in methanol. The linearity was obtained in the concentration range of 2-16 μg/ ml and 3-24 μg/ml for telmisartan and metoprolol succinate, respectively. The concentrations of the drugs were determined by using absorbance correction method at both the wavelengths. The method was successfully applied to pharmaceutical dosage form because no interference from the tablet excipients was found. The suitability of this method for the quantitative determination of telmisartan and metoprolol succinate was proved by validation. The proposed method was found to be simple and sensitive for the quality control application of telmisartan and metoprolol succinate in pharmaceutical dosage form. Result: The result of analysis has been validated statistically and by recovery studies. Recoveries were found in the range of 98.08-100.55% of telmisartan and 98.41-101.87% of metoprolol succinate. Key words: Absorbance correction, metoprolol succunate, spectrophotometry, telmisartan Komal Patel, Amit Patel, INTRODUCTION Jayant Dave, Chaganbhai Patel Telmisartan (TELM), 4’-[(1, 4’- dimethyl-2’-propyl [2, 6’-bi-1H benzimidazol]- Shri Saravajanik Pharmacy 1’-yl) methyl]-[1, 1’-biphenyl]-2-carboxylic acid, is an angiotensin II antagonist College, Mehasana, Gujarat, India [1-3] used as antihypertensive agent. TELMI blocks the vasoconstrictor and Address for correspondence: aldosterone secreting effects of angiotensin II by selectively blocking the Ms. Komal G. Patel, binding of angiotensin II to the AT1 receptor in many tissues, such as vascular Department of Quality Assurance, [4,5] Shri Saravajanik Pharmacy smooth muscle and the adrenal gland. Literature survey revealed that College, Near Arvind Baug, [6-12] [13] there are many developed methods on UV, visible spectrophotometric, Mehasana 384 001, Gujarat, India. [14,15] [16] [17] HPTLC, HPLC, and UPLC for estimation of TELM, single as well as E-mail: komalpatel112@rediffmail. com in combination. Metoprolol succinate (METO), 2-Propanol,1-[4-(2-methoxyethyl)phenoxy]-3-[(1- Access this article online methylethyl)amino]-(±) butanedioate succinate (2:1) (salt) is a cardioselective Website: www.phmethods.org β-blocker used in the management of hypertension, angina pectoris, cardiac DOI: 10.4103/2229-4708.103891 [18] arrhythmias, myocardial infarction and heart failure. Literature survey revealed [19-23] [24,25] [26-31] Quick response code that there are many developed methods on UV, HPTLC, HPLC, for estimation of METO single as well as in combination. However, there have been no reports concerning the simultaneous determination of (Figure 1) and (Figure 2) TELMI by absorbance correction method. These method was developed and validated as per International Conference on [32] Harmonization (ICH) guidelines. Pharmaceutical Methods | July-December 2012 | Vol 3 | Issue 2 Abstract Patel, et al.: Absorbance correction method of TELM and METO Figure 2: Chemical Structure of Telmisartan (TELM) Figure 1: Chemical structure of Metoprolol succinate (METO) MATERIALS AND METHODS Apparatus A s himadzu m odel 1800 (SHIM ADZU CORPORATION, International Marketing Division, Figure 3: Simple overlay spectra of TELM (2-16µg/ml) and METO (3-24 µg/ml) in methanol Japan) double beam UV/Visible spectrophotometer with spectral width of 2 nm, wavelength accuracy having concentration of TELM (100 μg/ml) and METO of 0.5 nm and a pair of 10 mm matched quartz cell (100 μg/ml). was used to measure absorbance of all the solutions. Spectra were automatically obtained by UV-Probe system software (UV Probe version 2.31). Digital Absorbance correction method balance Acculab (ALC 210.4) and Sonicator Eneritech The value of λ of was determined by scanning the max (Ultra Sonicator) was used in the study. drug solution in the range 200-400nm at 0.5 band width and 600 nm/min scan speed and was found to be Material at 296 nm and 223 nm, respectively. TELM also showed Active pharmaceutical ingredient of TELM and METO absorbance at 223 nm, while METO did not show any were supplied by Zydus Cadila Healthcare Ltd., interference at 296 nm. [Figure 3] To construct Beer ’s Ahmedabad, Gujarat, India. plot for TELM and METO, stock solutions of both the drugs were prepared in methanol [100 μg/ml]. Also Marketed formulation Beer ’s plot was constructed for TELM and METO in TELSAR BETA (UNICHEM LABORATORIES, India) solution mixture at different concentration. Both the contains TELM IP 40 mg and METO USP 50 mg. drugs followed linearity individually in TELM (2, 4, 6, 8, 10, 12, 14, 16 μg/ml) and METO (3, 6, 9, 12, 15, 18, Other formulation Telmaxx 50 (GLENMARK 21, 24 μg/ml) and in mixture with the concentration pharmaceutical Ltd., Mumbai) was purchased from range TELM:METO are (1:1.25, 2:2.5, 3:3.75, 4:5, 5:6.25, an open market for this study which contains TELM 6:7.5, 7:8.75 μg/ml). IP 40 mg and METO USP 50 mg [Table 3]. The concentration of two drugs in the mixture can be Reagent and chemical calculated using following equations Methanol was used as a solvent which was procured from Finar Chemicals Ltd., Ahmedabad, India. Double A = abc distilled water was used throughout the analysis. Cx = A1 / ab Cx = A1 / ax1 * b (1) Preparation of standard stock solution A2 = A Telm + A meto An accurately weighed quantity of TELM (10 mg) and METO (10 mg) were transferred to a separate A2 = (ay2 * cy * b) + (ax2 * cx * b) 100 ml volumetric flask and dissolved and diluted to A2 = (ay2 * cy) + (ax2 * cx) the mark with methanol to obtain standard solution Cy = [A2 - (ax2 * cx)] / ay2 (2) Pharmaceutical Methods | July-December 2012 | Vol 3 | Issue 2 107 Patel, et al.: Absorbance correction method of TELM and METO where A , A are absorbance of mixture at 296 nm (A1) and 223nm (A2). The results were reported in 1 2 (λ ) and 223 nm (λ ), respectively, ax and ax are terms of relative standard deviation. 1 2 1 2 absorptivities of TELM at λ and λ , respectively, 1 2 ay and ay are absorptivities of METO at λ and λ , 1 2 1 2 Method precision respectively, c and c are concentrations of TELM and x y Intraday METO, respectively. Test solutions containing 2, 4, 6 μg/ml TELM and 2.5, 5.0, 7.5 μg/ml of METO was analyzed three times on Validation of proposed method the same day. Measure the solution at 296 nm (A1) Linearity (Calibration curve) and 223 nm (A2). The results were reported in terms The calibration curves were plotted over a concentration of relative standard deviation. range of 2-16 μg/ml for TELM and 3-24 μg/ml METO. Accurately measured standard stock solutions of Interday each TELM (0.2, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4 and 1.6 Test solution containing 2, 4, 6 μg/ml TELM and 2.5, ml) and METO (0.3, 0.6, 0.9, 1.2, 1.5, 1.8, 2.1, 2.4) 5.0, 7.5 μg/ml of METO was analyzed on 3 different were transferred to a series of 10 ml volumetric days. Measure the solution at 296 nm (A1) and 223 nm flask separately and diluted up to the mark with (A2). The results were reported in terms of relative methanol. The absorbances of solution were then standard deviation. measured at 296 nm and 223 nm. The calibration curves were constructed by plotting absorbances versus concentration and the regression equations Specificity were calculated. Specificity is a procedure to detect quantitatively the analyte in presence of component that may be expected to be present in the sample matrix. Commonly used Precision excipients in tablet preparation were spiked in a System precision preweight quantity of drug and then absorbance was Intraday Mixed standard solutions containing 2, 4, 6 μg/ml measured and calculation done to determine quantity TELM and 2.5, 5.0, 7.5 μg/ml of METO was analyzed of drugs. [Figure 6] three times on the same day. Measure the solution at 296 nm (A1) and 223 nm (A2). The results were Accuracy reported in terms of relative standard deviation. The accuracy of the method was determined by calculating recoveries of TELM and METO by the Interday standard addition method. Accuracy is performed Mixed standard solution containing 2, 4, 6 μg/ml at three levels 25, 50 and 75%. Known amount of TELM and 2.5, 5.0, 7.5 μg/ml of METO was analyzed standard solutions of TELM (0, 1, 2 and 3 μg/ml) on 3 different days. Measure the solution at 296 nm and METO (0, 1.25, 2.5 and 3.75 μg/ml) were added to a pre-quantified test solution of TELM (4 μg/mL) and METO (5 μg/mL). Absorbance of solution was measured at selected wavelength for TELM and METO. The amount of TELM and METO was calculated at each level by absorbance correction equation method and % recoveries were computed. Figure 4: Calibration curve for TELM Figure 6: UV spectrum showing standard mixture of TELM and METO Figure 5: Calibration curve for METO (4:5 µg/ml), test sample of TELM and METO (4:5 µg/ml), and placebo. Pharmaceutical Methods | July-December 2012 | Vol 3 | Issue 2 108 Patel, et al.: Absorbance correction method of TELM and METO Limit of detection and limit of quantitation calibration curves were prepared for both the drugs. Limit of detection is the lowest amount of analyte in The overlain UV absorption spectra of TELM (296 nm) a sample which can be detected but not necessarily and METO (223 nm) in methanol is shown in [Figure 4 quantitated as an exact value and limit of quantitation and 5]. The validation parameters were studied at all the wavelengths for the proposed method [Table 1]. is the lowest amount of analyte in a sample which can be quantitatively determined with suitable precision Accuracy was determined by calculating the recovery [32] and the mean was determined [Table 2]. The method and accuracy. For these prepare linearity at the was successfully used to determine the amounts of lowest concentration mixture containing TELM (0.16 - TELM and METO present in the tablet dosage forms. 0.24 μg/ml) and METO (0.2 - 0.3 μg/ml) and measure The results obtained were in good agreement with The absorbance at 296 nm and 223 nm. Plot the the corresponding labeled amount [Table 3]. Precision calibration curve of absorbance vs concentration for was calculated as repeatability and intra and interday individual wavelength and determine regression line variations (% RSD) for both the drugs. equations for TELM and METO and find out the the limit of detection (LOD) and the limit of quantification (LOQ) were calculated using the standard deviation CONCLUSIONS of repeatability and slope (S) of the calibration of new calibration curve for LOD and LOQ. The developed absorbance correction method is found to be simple, sensitive, accurate and precise and can 33 . × N LOD= Table 1: Regression analysis data and summary of validation parameters for the proposed method 10 × N LOQ= Parameters TELM METO Wavelength range (nm) 296 223 Beer’s law limit (μg/ml) 4-16 6-24 where, N = the standard deviation of the response and S = slope of the calibration curve. Regression equation y = 0.050x + y = 0.031x + (y = mx + c) 0.003 0.029 Slope 0.050 0.031 Analysis of TELM and METO in combined tablet Intercept 0.003 0.029 Twenty tablets were weighed and the average weight [2] Correlation Coefficient (r ) 0.9999 0.9998 was calculated. The tablet powder equivalent to 10 System precision (%R.S.D) mg of TELM and 12.5 mg of METO were weighed 0.79-1.45 0.17-0.53 and transferred to 100 ml volumetric flask. Methanol 1. Intraday precision(n = 3) 0.66-1.46 0.20-0.72 2. Interday precision(n = 3) (50 ml) was added and sonicated for 20 min. The 0.28-1.03 Method precision (%R.S.D) volume is adjusted up to the mark with methanol. 0.48-1.45 0.23-0.92 1. Intraday precision(n = 3) 0.96-1.49 The solution was then filtered through Whatman filter 2. Interday precision(n = 3) paper no. 41. The solution was suitably diluted with Accuracy (% recovery) 98.08- 98.41- methanol to get a final concentration of 4 μg/ml of (n = 3) 100.55% 101.87% TELM and 5 μg/ml of METO. The absorbances of the LOD (μg/ml) 0.055 0.015 sample solution i.e. A1 and A2 were recorded at 296 LOQ (μg/ml) 0.166 0.045 nm (λ-max of TELM) and 223 nm (λ-max of METO) Assay (±S.D.) (n = 3) 99.0 ± 0.22 98.6 ± 1.12 respectively, Relative concentration of two drugs in a b c RSD = Relative standard deviation. LOD = Limit of detection. LOQ = Limit of the sample was calculated using above equation (1) quantitation SD is Standard deviation and n is number of replicates. and (2). Table 2: Recovery data of proposed method RESULTS AND DISCUSSION Drug Amount Amount Amount %Mean taken added added recovery (μg/ml) (μg/ml) (%) (±S.D.) (n = 3) In absorbance correction method, the primary 4 1 25 99.74 ± 1.74 requirement for developing a method for analysis is TELM 4 2 50 98.08 ± 1.18 that the entire spectra should follow the Beer’s law 4 3 75 100.55 ± 1.36 [16] at all the wavelength, which was fulfilled in case 5 1.25 25 101.87 ± 0.43 of both these drugs. The two wavelengths were used 5 2.5 50 100.13 ± 0.86 METO for the analysis of the drugs were 296 nm (λ-max of 5 3.75 75 98.41 ± 1.12 TELM) and 223 nm (λ-max of METO) at which the S.D is Standard deviation and n is number of replicates Pharmaceutical Methods | July-December 2012 | Vol 3 | Issue 2 109 Patel, et al.: Absorbance correction method of TELM and METO Table 3: Analysis of TELM and METO by proposed method Tablet Labelled claim (mg) Amount found (mg) % Label claim (±S. D.) (n = 3) TELM METO TELM METO TELM METO I (TELSAR BETA) 40 50 39.60 49.30 99.00 ± 0.22 98.60 ± 1.12 II (Telmaxx 50) 40 50 39.51 49.27 98.77 ± 0.87 98.54 ± 1.23 S.D. is Standard deviation and n is number of replicates 13. Kumbhar ST, Chougule GK, Gajeli GB, Tegeli VS, Thorat YS, be used for routine analysis of TELM and METO. Shivsharan US. Visible spectrophotometric determination of The developed method was validated as par ICH telmisartan from urine. Int J Pharm Sci Res 2011;2:1254-8. guidelines. Statistical analysis proved that the method 14. Prabhu C, Subramanian GS, Karthik A, Kini S, Rajan MS, Udupa N. is repeatable and selective for the analysis of TELM Determination of telmisartan by HPTLC – a stability indicating assay. J Planar Chromatogr 2007;20:477-81. and METO in combination as a single drug in bulk as 15. Chabukswar AR, Jagdale SC, Kumbhar SV, Kadam VJ, Patil VD, well as in pharmaceutical formulations. Kuchekar BS, et al. Simultaneous HPTLC estimation of telmisartan and amlodipine besylate in tablet dosage form. Scholars Research Library. Arch Appl Sci Res 2010;2:94-100. ACKNOWLEDGMENT 16. Palled MS, Chatter M, Rajesh PM, Bhat AR. RP-HPLC Determination of telmisartan in tablet dosage forms. Indian J Pharm Sci 2005;67:108-9. The authors are thankful to Corona Zydus Cadila 17. Nalwade S, Reddy VR, Rao DD, Rao IK. Rapid simultaneous Healthcare Ltd. Ahmedabad, Gujarat, India for providing determination of telmisartan, amlodipine besylate and gift sample of TELM and METO for research. The authors hydrochlorothiazide in a combined poly pill dosage form by are highly thankful to Shri Sarvajanik Pharmacy College, stability-indicating ultra performance liquid chromatography. Sci Mehsana, Gujarat, India for providing all the facilities to Pharm 2011;79:69-84. carry out the work. 18. United States Pharmacopoeia, United States Pharmacopoeial Convention, Rockville, MD, 2007, Vol. 2, p. 1279 - 1280. 19. Sawant SD, Ghante MR, Deshpande AS, Shah B. Three simple REFERENCES spectrometric methods for metoprolol succinate in tablet form. Int J Chem and Anal Sci 2010;1:217-8. th 20. Kulkarni MN, Kshirsagar RV, Sakarkar DM. Development and 1. Budavari S, editor. In: The Merck Index. 13 ed. White House Station, validation of spectrophotometric method for determination of NJ: Merck and Co. Inc.; 2001. p. 1628. metoprolol succinate. Int J Chem Tech Res 2009;1:1273-7. 2. Indian Pharmacopoeia. Government of India Ministry of Health 21. Wankhede SB, Dixit NR, Chitlange SS. Validated spectrophotometric and Family Welfare. Vol. 3. New Delhi: The Indian Pharmacopoeia Commission; 2010. pp. 2186-7. methods for quantitative determination of atorvastatin calcium and 3. British pharmacopoeia. Vol. 2. London: Her Majesty’s stationary metoprolol succinate in capsules. Scholars Res Library Der Pharm Office; 2009. p. 5872-7. Chem 2010;2:134-40. th 4. Ean CS, Martindale. The Complete Drug Reference. 36 ed. London: 22. Rath S, Panda SK, Sarangi RR, Dash A, Rath SK, Nayak S. UV- The Pharmaceutical Press; 2009. p. 1409. spectrophotometric method for simultaneous estimation of 5. Anon. Pharmacy and Theraputics Review-Telmisartan. The metoprolol and amlodipine in bulk and their formulation. Int J Biol Formulary, Jan 1999. p. 13. Pharm Res 2011;2:50-4. 6. Palled MS, Chatter M, Rajesh PM, Bhat AR. Difference 23. Vachhani KH, Patel SA. Development and validation of spectrophotometric determination of telmisartan in tablet dosage spectrophotometric method for simultaneous estimation of forms. Indian J Pharm Sci 2006;68:685-6. metoprolol succinate and olmesartan medoxomil in tablet. J App 7. Tatane S. Glenmark Pharmaceuticals Limited, Sinnar Nashik. Pharm Sci 2011;1:112-5. Development of UV spectrophotometric method of telmisartan in 24. Sathe SR, Bari SB, Surana SJ. Development of HPTLC method for the tablet formulation. J Adv Pharm Healthc Res 2011;1:23-6. estimation of metoprolol succinate in bulk and in tablet dosage form. 8. Bebawy LI, Abbas SS, Fattah LA, Refaat HH. Application of first- Indian J Pharm Edu and Res 2008;42:32-5. derivative, ratio derivative spectrophotometry, TLC-densitometry 25. Wankhede SB, Dixit NR, Chitlange SS. Stability indicating HPTLC and spectrofluorimetry for the simultaneous, determination of method for quantitative determination of atorvastatin calcium and telmisartan and hydrochlorothiazide in pharmaceutical dosage metoprolol succinate in Capsules. Scholars Res Library Der Pharm forms and plasma. Farmaco 2005;60:859-67. Lett 2011;3:1-7. 9. Kondawar MS, Kamble KG, Raut KS, Maharshi KH. UV 26. Phale MD, Hamrapurkar PD. A validated and simplified RP- spectrophotometric estimation of amlodipine besylate and HPLC of metoprolol succinate from bulk drugs. Asian J Res Chem telmisartan in bulk drug and dosage form by multiwavelength 2009;2:119-22. analysis. Int J ChemTech Res 2011;3:1274-80. 27. Singh B, Patel DK, Ghosh SK. Development of RP HPLC 10. Gangola R, Singh N, Gaurav A, Maithani M, Singh R. Spectrophotometric method for simultaneous analysis of metoprolol succinate and simultaneous determination of hydrochlorothiazide and telmisartan hydrochlorothiazide in a tablet formulation. Trop J Pharm Res in combined dosage form by dual wavelength method. Int J 2009;8:539-43. Comprehens Pharm 2011;2:1-3. 28. Dongre VG, Shah SB, Karmuse PP, Phadke M, Jadhav VK. 11. Ilingo K, Shiji Kumar PS. Simultaneous estimation of telmisartan Simultaneous determination of metoprolol succinate and amlodipine and hydrochlorothiazide in pharmaceutical dosage form. Asian J besylate in pharmaceutical dosage form by HPLC. J Pharm Biomed Pharm Health Sci 2011;1:12-5. Anal 2008;46:583-6. 12. Thomas AB, Jagdale SN, Dighe SB, Nanda RK. Simultaneous 29. Rajamanickam V, Rathinaraj BS, Thangavelpandian N, Pandian AR. spectrophotometric estimation of amlodipine besylate and A validated RP-HPLC method of metoprolol Succinate and telmisartan in tablet dosage form. Int J Chem Tech Res 2010;2: amlodipine Succinate from bulk drugs. Scholars Res Library Der 1334-41. Pharmaceutical Methods | July-December 2012 | Vol 3 | Issue 2 110 Patel, et al.: Absorbance correction method of TELM and METO Pharm Lett 2010;2:40-6. 32. ICH Q2 (R1), Harmonizazed Tripatite Guidline, Validation of 30. Rao MM, Rahaman SA, Prasad YR, Reddy PG. RP-HPLC method Analytical Procedure: Text and Methodology, 2005. of Simultaneous estimation of amlodipine Besylate and metoprolol in combined dosage form. Int J Pharm Res Dev-Online 2010; How to cite this article: Patel K, Patel A, Dave J, Patel C. 2:69-72. Absorbance correction method for estimation of telmisartan and 31. Joshi P, Kumar M, Development and validation of a reverse phase metoprolol succinate in combined tablet dosage forms. Pharm HPLC method for the simultaneous estimation of metoprolol and Methods 2012;3:106-11. telmisartan in tablet dosage form. Pelagia Res Library, Der Pharm Source of Support: Nil, Conflict of Interest: None declared. Sinica 2011;2:211-9. Pharmaceutical Methods | July-December 2012 | Vol 3 | Issue 2 http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Pharmaceutical Methods Pubmed Central

Absorbance correction method for estimation of telmisartan and metoprolol succinate in combined tablet dosage forms

Pharmaceutical Methods , Volume 3 (2) – Aug 1, 168

Loading next page...
 
/lp/pubmed-central/absorbance-correction-method-for-estimation-of-telmisartan-and-YlQG3Xc9iD

References (28)

Publisher
Pubmed Central
Copyright
Copyright: © Pharmaceutical Methods
ISSN
2229-4708
eISSN
2229-4716
DOI
10.4103/2229-4708.103891
Publisher site
See Article on Publisher Site

Abstract

Original Article Absorbance correction method for estimation of telmisartan and metoprolol succinate in combined tablet dosage forms Aim and Background: The present manuscript describes simple, sensitive, rapid, accurate, precise and economical spectrophotometric method for the simultaneous determination of telmisartan and metoprolol succinate in combined tablet dosage form. Materials and Methods: The method is based on the absorbance correction equations for analysis of both the drugs using methanol as solvent. Telmisartan has absorbance maxima at 296 nm and metoprolol succinate has absorbance maxima at 223 nm in methanol. The linearity was obtained in the concentration range of 2-16 μg/ ml and 3-24 μg/ml for telmisartan and metoprolol succinate, respectively. The concentrations of the drugs were determined by using absorbance correction method at both the wavelengths. The method was successfully applied to pharmaceutical dosage form because no interference from the tablet excipients was found. The suitability of this method for the quantitative determination of telmisartan and metoprolol succinate was proved by validation. The proposed method was found to be simple and sensitive for the quality control application of telmisartan and metoprolol succinate in pharmaceutical dosage form. Result: The result of analysis has been validated statistically and by recovery studies. Recoveries were found in the range of 98.08-100.55% of telmisartan and 98.41-101.87% of metoprolol succinate. Key words: Absorbance correction, metoprolol succunate, spectrophotometry, telmisartan Komal Patel, Amit Patel, INTRODUCTION Jayant Dave, Chaganbhai Patel Telmisartan (TELM), 4’-[(1, 4’- dimethyl-2’-propyl [2, 6’-bi-1H benzimidazol]- Shri Saravajanik Pharmacy 1’-yl) methyl]-[1, 1’-biphenyl]-2-carboxylic acid, is an angiotensin II antagonist College, Mehasana, Gujarat, India [1-3] used as antihypertensive agent. TELMI blocks the vasoconstrictor and Address for correspondence: aldosterone secreting effects of angiotensin II by selectively blocking the Ms. Komal G. Patel, binding of angiotensin II to the AT1 receptor in many tissues, such as vascular Department of Quality Assurance, [4,5] Shri Saravajanik Pharmacy smooth muscle and the adrenal gland. Literature survey revealed that College, Near Arvind Baug, [6-12] [13] there are many developed methods on UV, visible spectrophotometric, Mehasana 384 001, Gujarat, India. [14,15] [16] [17] HPTLC, HPLC, and UPLC for estimation of TELM, single as well as E-mail: komalpatel112@rediffmail. com in combination. Metoprolol succinate (METO), 2-Propanol,1-[4-(2-methoxyethyl)phenoxy]-3-[(1- Access this article online methylethyl)amino]-(±) butanedioate succinate (2:1) (salt) is a cardioselective Website: www.phmethods.org β-blocker used in the management of hypertension, angina pectoris, cardiac DOI: 10.4103/2229-4708.103891 [18] arrhythmias, myocardial infarction and heart failure. Literature survey revealed [19-23] [24,25] [26-31] Quick response code that there are many developed methods on UV, HPTLC, HPLC, for estimation of METO single as well as in combination. However, there have been no reports concerning the simultaneous determination of (Figure 1) and (Figure 2) TELMI by absorbance correction method. These method was developed and validated as per International Conference on [32] Harmonization (ICH) guidelines. Pharmaceutical Methods | July-December 2012 | Vol 3 | Issue 2 Abstract Patel, et al.: Absorbance correction method of TELM and METO Figure 2: Chemical Structure of Telmisartan (TELM) Figure 1: Chemical structure of Metoprolol succinate (METO) MATERIALS AND METHODS Apparatus A s himadzu m odel 1800 (SHIM ADZU CORPORATION, International Marketing Division, Figure 3: Simple overlay spectra of TELM (2-16µg/ml) and METO (3-24 µg/ml) in methanol Japan) double beam UV/Visible spectrophotometer with spectral width of 2 nm, wavelength accuracy having concentration of TELM (100 μg/ml) and METO of 0.5 nm and a pair of 10 mm matched quartz cell (100 μg/ml). was used to measure absorbance of all the solutions. Spectra were automatically obtained by UV-Probe system software (UV Probe version 2.31). Digital Absorbance correction method balance Acculab (ALC 210.4) and Sonicator Eneritech The value of λ of was determined by scanning the max (Ultra Sonicator) was used in the study. drug solution in the range 200-400nm at 0.5 band width and 600 nm/min scan speed and was found to be Material at 296 nm and 223 nm, respectively. TELM also showed Active pharmaceutical ingredient of TELM and METO absorbance at 223 nm, while METO did not show any were supplied by Zydus Cadila Healthcare Ltd., interference at 296 nm. [Figure 3] To construct Beer ’s Ahmedabad, Gujarat, India. plot for TELM and METO, stock solutions of both the drugs were prepared in methanol [100 μg/ml]. Also Marketed formulation Beer ’s plot was constructed for TELM and METO in TELSAR BETA (UNICHEM LABORATORIES, India) solution mixture at different concentration. Both the contains TELM IP 40 mg and METO USP 50 mg. drugs followed linearity individually in TELM (2, 4, 6, 8, 10, 12, 14, 16 μg/ml) and METO (3, 6, 9, 12, 15, 18, Other formulation Telmaxx 50 (GLENMARK 21, 24 μg/ml) and in mixture with the concentration pharmaceutical Ltd., Mumbai) was purchased from range TELM:METO are (1:1.25, 2:2.5, 3:3.75, 4:5, 5:6.25, an open market for this study which contains TELM 6:7.5, 7:8.75 μg/ml). IP 40 mg and METO USP 50 mg [Table 3]. The concentration of two drugs in the mixture can be Reagent and chemical calculated using following equations Methanol was used as a solvent which was procured from Finar Chemicals Ltd., Ahmedabad, India. Double A = abc distilled water was used throughout the analysis. Cx = A1 / ab Cx = A1 / ax1 * b (1) Preparation of standard stock solution A2 = A Telm + A meto An accurately weighed quantity of TELM (10 mg) and METO (10 mg) were transferred to a separate A2 = (ay2 * cy * b) + (ax2 * cx * b) 100 ml volumetric flask and dissolved and diluted to A2 = (ay2 * cy) + (ax2 * cx) the mark with methanol to obtain standard solution Cy = [A2 - (ax2 * cx)] / ay2 (2) Pharmaceutical Methods | July-December 2012 | Vol 3 | Issue 2 107 Patel, et al.: Absorbance correction method of TELM and METO where A , A are absorbance of mixture at 296 nm (A1) and 223nm (A2). The results were reported in 1 2 (λ ) and 223 nm (λ ), respectively, ax and ax are terms of relative standard deviation. 1 2 1 2 absorptivities of TELM at λ and λ , respectively, 1 2 ay and ay are absorptivities of METO at λ and λ , 1 2 1 2 Method precision respectively, c and c are concentrations of TELM and x y Intraday METO, respectively. Test solutions containing 2, 4, 6 μg/ml TELM and 2.5, 5.0, 7.5 μg/ml of METO was analyzed three times on Validation of proposed method the same day. Measure the solution at 296 nm (A1) Linearity (Calibration curve) and 223 nm (A2). The results were reported in terms The calibration curves were plotted over a concentration of relative standard deviation. range of 2-16 μg/ml for TELM and 3-24 μg/ml METO. Accurately measured standard stock solutions of Interday each TELM (0.2, 0.4, 0.6, 0.8, 1.0, 1.2, 1.4 and 1.6 Test solution containing 2, 4, 6 μg/ml TELM and 2.5, ml) and METO (0.3, 0.6, 0.9, 1.2, 1.5, 1.8, 2.1, 2.4) 5.0, 7.5 μg/ml of METO was analyzed on 3 different were transferred to a series of 10 ml volumetric days. Measure the solution at 296 nm (A1) and 223 nm flask separately and diluted up to the mark with (A2). The results were reported in terms of relative methanol. The absorbances of solution were then standard deviation. measured at 296 nm and 223 nm. The calibration curves were constructed by plotting absorbances versus concentration and the regression equations Specificity were calculated. Specificity is a procedure to detect quantitatively the analyte in presence of component that may be expected to be present in the sample matrix. Commonly used Precision excipients in tablet preparation were spiked in a System precision preweight quantity of drug and then absorbance was Intraday Mixed standard solutions containing 2, 4, 6 μg/ml measured and calculation done to determine quantity TELM and 2.5, 5.0, 7.5 μg/ml of METO was analyzed of drugs. [Figure 6] three times on the same day. Measure the solution at 296 nm (A1) and 223 nm (A2). The results were Accuracy reported in terms of relative standard deviation. The accuracy of the method was determined by calculating recoveries of TELM and METO by the Interday standard addition method. Accuracy is performed Mixed standard solution containing 2, 4, 6 μg/ml at three levels 25, 50 and 75%. Known amount of TELM and 2.5, 5.0, 7.5 μg/ml of METO was analyzed standard solutions of TELM (0, 1, 2 and 3 μg/ml) on 3 different days. Measure the solution at 296 nm and METO (0, 1.25, 2.5 and 3.75 μg/ml) were added to a pre-quantified test solution of TELM (4 μg/mL) and METO (5 μg/mL). Absorbance of solution was measured at selected wavelength for TELM and METO. The amount of TELM and METO was calculated at each level by absorbance correction equation method and % recoveries were computed. Figure 4: Calibration curve for TELM Figure 6: UV spectrum showing standard mixture of TELM and METO Figure 5: Calibration curve for METO (4:5 µg/ml), test sample of TELM and METO (4:5 µg/ml), and placebo. Pharmaceutical Methods | July-December 2012 | Vol 3 | Issue 2 108 Patel, et al.: Absorbance correction method of TELM and METO Limit of detection and limit of quantitation calibration curves were prepared for both the drugs. Limit of detection is the lowest amount of analyte in The overlain UV absorption spectra of TELM (296 nm) a sample which can be detected but not necessarily and METO (223 nm) in methanol is shown in [Figure 4 quantitated as an exact value and limit of quantitation and 5]. The validation parameters were studied at all the wavelengths for the proposed method [Table 1]. is the lowest amount of analyte in a sample which can be quantitatively determined with suitable precision Accuracy was determined by calculating the recovery [32] and the mean was determined [Table 2]. The method and accuracy. For these prepare linearity at the was successfully used to determine the amounts of lowest concentration mixture containing TELM (0.16 - TELM and METO present in the tablet dosage forms. 0.24 μg/ml) and METO (0.2 - 0.3 μg/ml) and measure The results obtained were in good agreement with The absorbance at 296 nm and 223 nm. Plot the the corresponding labeled amount [Table 3]. Precision calibration curve of absorbance vs concentration for was calculated as repeatability and intra and interday individual wavelength and determine regression line variations (% RSD) for both the drugs. equations for TELM and METO and find out the the limit of detection (LOD) and the limit of quantification (LOQ) were calculated using the standard deviation CONCLUSIONS of repeatability and slope (S) of the calibration of new calibration curve for LOD and LOQ. The developed absorbance correction method is found to be simple, sensitive, accurate and precise and can 33 . × N LOD= Table 1: Regression analysis data and summary of validation parameters for the proposed method 10 × N LOQ= Parameters TELM METO Wavelength range (nm) 296 223 Beer’s law limit (μg/ml) 4-16 6-24 where, N = the standard deviation of the response and S = slope of the calibration curve. Regression equation y = 0.050x + y = 0.031x + (y = mx + c) 0.003 0.029 Slope 0.050 0.031 Analysis of TELM and METO in combined tablet Intercept 0.003 0.029 Twenty tablets were weighed and the average weight [2] Correlation Coefficient (r ) 0.9999 0.9998 was calculated. The tablet powder equivalent to 10 System precision (%R.S.D) mg of TELM and 12.5 mg of METO were weighed 0.79-1.45 0.17-0.53 and transferred to 100 ml volumetric flask. Methanol 1. Intraday precision(n = 3) 0.66-1.46 0.20-0.72 2. Interday precision(n = 3) (50 ml) was added and sonicated for 20 min. The 0.28-1.03 Method precision (%R.S.D) volume is adjusted up to the mark with methanol. 0.48-1.45 0.23-0.92 1. Intraday precision(n = 3) 0.96-1.49 The solution was then filtered through Whatman filter 2. Interday precision(n = 3) paper no. 41. The solution was suitably diluted with Accuracy (% recovery) 98.08- 98.41- methanol to get a final concentration of 4 μg/ml of (n = 3) 100.55% 101.87% TELM and 5 μg/ml of METO. The absorbances of the LOD (μg/ml) 0.055 0.015 sample solution i.e. A1 and A2 were recorded at 296 LOQ (μg/ml) 0.166 0.045 nm (λ-max of TELM) and 223 nm (λ-max of METO) Assay (±S.D.) (n = 3) 99.0 ± 0.22 98.6 ± 1.12 respectively, Relative concentration of two drugs in a b c RSD = Relative standard deviation. LOD = Limit of detection. LOQ = Limit of the sample was calculated using above equation (1) quantitation SD is Standard deviation and n is number of replicates. and (2). Table 2: Recovery data of proposed method RESULTS AND DISCUSSION Drug Amount Amount Amount %Mean taken added added recovery (μg/ml) (μg/ml) (%) (±S.D.) (n = 3) In absorbance correction method, the primary 4 1 25 99.74 ± 1.74 requirement for developing a method for analysis is TELM 4 2 50 98.08 ± 1.18 that the entire spectra should follow the Beer’s law 4 3 75 100.55 ± 1.36 [16] at all the wavelength, which was fulfilled in case 5 1.25 25 101.87 ± 0.43 of both these drugs. The two wavelengths were used 5 2.5 50 100.13 ± 0.86 METO for the analysis of the drugs were 296 nm (λ-max of 5 3.75 75 98.41 ± 1.12 TELM) and 223 nm (λ-max of METO) at which the S.D is Standard deviation and n is number of replicates Pharmaceutical Methods | July-December 2012 | Vol 3 | Issue 2 109 Patel, et al.: Absorbance correction method of TELM and METO Table 3: Analysis of TELM and METO by proposed method Tablet Labelled claim (mg) Amount found (mg) % Label claim (±S. D.) (n = 3) TELM METO TELM METO TELM METO I (TELSAR BETA) 40 50 39.60 49.30 99.00 ± 0.22 98.60 ± 1.12 II (Telmaxx 50) 40 50 39.51 49.27 98.77 ± 0.87 98.54 ± 1.23 S.D. is Standard deviation and n is number of replicates 13. Kumbhar ST, Chougule GK, Gajeli GB, Tegeli VS, Thorat YS, be used for routine analysis of TELM and METO. Shivsharan US. Visible spectrophotometric determination of The developed method was validated as par ICH telmisartan from urine. Int J Pharm Sci Res 2011;2:1254-8. guidelines. Statistical analysis proved that the method 14. Prabhu C, Subramanian GS, Karthik A, Kini S, Rajan MS, Udupa N. is repeatable and selective for the analysis of TELM Determination of telmisartan by HPTLC – a stability indicating assay. J Planar Chromatogr 2007;20:477-81. and METO in combination as a single drug in bulk as 15. Chabukswar AR, Jagdale SC, Kumbhar SV, Kadam VJ, Patil VD, well as in pharmaceutical formulations. Kuchekar BS, et al. Simultaneous HPTLC estimation of telmisartan and amlodipine besylate in tablet dosage form. Scholars Research Library. Arch Appl Sci Res 2010;2:94-100. ACKNOWLEDGMENT 16. Palled MS, Chatter M, Rajesh PM, Bhat AR. RP-HPLC Determination of telmisartan in tablet dosage forms. Indian J Pharm Sci 2005;67:108-9. The authors are thankful to Corona Zydus Cadila 17. Nalwade S, Reddy VR, Rao DD, Rao IK. Rapid simultaneous Healthcare Ltd. Ahmedabad, Gujarat, India for providing determination of telmisartan, amlodipine besylate and gift sample of TELM and METO for research. The authors hydrochlorothiazide in a combined poly pill dosage form by are highly thankful to Shri Sarvajanik Pharmacy College, stability-indicating ultra performance liquid chromatography. Sci Mehsana, Gujarat, India for providing all the facilities to Pharm 2011;79:69-84. carry out the work. 18. United States Pharmacopoeia, United States Pharmacopoeial Convention, Rockville, MD, 2007, Vol. 2, p. 1279 - 1280. 19. Sawant SD, Ghante MR, Deshpande AS, Shah B. Three simple REFERENCES spectrometric methods for metoprolol succinate in tablet form. Int J Chem and Anal Sci 2010;1:217-8. th 20. Kulkarni MN, Kshirsagar RV, Sakarkar DM. Development and 1. Budavari S, editor. In: The Merck Index. 13 ed. White House Station, validation of spectrophotometric method for determination of NJ: Merck and Co. Inc.; 2001. p. 1628. metoprolol succinate. Int J Chem Tech Res 2009;1:1273-7. 2. Indian Pharmacopoeia. Government of India Ministry of Health 21. Wankhede SB, Dixit NR, Chitlange SS. Validated spectrophotometric and Family Welfare. Vol. 3. New Delhi: The Indian Pharmacopoeia Commission; 2010. pp. 2186-7. methods for quantitative determination of atorvastatin calcium and 3. British pharmacopoeia. Vol. 2. London: Her Majesty’s stationary metoprolol succinate in capsules. Scholars Res Library Der Pharm Office; 2009. p. 5872-7. Chem 2010;2:134-40. th 4. Ean CS, Martindale. The Complete Drug Reference. 36 ed. London: 22. Rath S, Panda SK, Sarangi RR, Dash A, Rath SK, Nayak S. UV- The Pharmaceutical Press; 2009. p. 1409. spectrophotometric method for simultaneous estimation of 5. Anon. Pharmacy and Theraputics Review-Telmisartan. The metoprolol and amlodipine in bulk and their formulation. Int J Biol Formulary, Jan 1999. p. 13. Pharm Res 2011;2:50-4. 6. Palled MS, Chatter M, Rajesh PM, Bhat AR. Difference 23. Vachhani KH, Patel SA. Development and validation of spectrophotometric determination of telmisartan in tablet dosage spectrophotometric method for simultaneous estimation of forms. Indian J Pharm Sci 2006;68:685-6. metoprolol succinate and olmesartan medoxomil in tablet. J App 7. Tatane S. Glenmark Pharmaceuticals Limited, Sinnar Nashik. Pharm Sci 2011;1:112-5. Development of UV spectrophotometric method of telmisartan in 24. Sathe SR, Bari SB, Surana SJ. Development of HPTLC method for the tablet formulation. J Adv Pharm Healthc Res 2011;1:23-6. estimation of metoprolol succinate in bulk and in tablet dosage form. 8. Bebawy LI, Abbas SS, Fattah LA, Refaat HH. Application of first- Indian J Pharm Edu and Res 2008;42:32-5. derivative, ratio derivative spectrophotometry, TLC-densitometry 25. Wankhede SB, Dixit NR, Chitlange SS. Stability indicating HPTLC and spectrofluorimetry for the simultaneous, determination of method for quantitative determination of atorvastatin calcium and telmisartan and hydrochlorothiazide in pharmaceutical dosage metoprolol succinate in Capsules. Scholars Res Library Der Pharm forms and plasma. Farmaco 2005;60:859-67. Lett 2011;3:1-7. 9. Kondawar MS, Kamble KG, Raut KS, Maharshi KH. UV 26. Phale MD, Hamrapurkar PD. A validated and simplified RP- spectrophotometric estimation of amlodipine besylate and HPLC of metoprolol succinate from bulk drugs. Asian J Res Chem telmisartan in bulk drug and dosage form by multiwavelength 2009;2:119-22. analysis. Int J ChemTech Res 2011;3:1274-80. 27. Singh B, Patel DK, Ghosh SK. Development of RP HPLC 10. Gangola R, Singh N, Gaurav A, Maithani M, Singh R. Spectrophotometric method for simultaneous analysis of metoprolol succinate and simultaneous determination of hydrochlorothiazide and telmisartan hydrochlorothiazide in a tablet formulation. Trop J Pharm Res in combined dosage form by dual wavelength method. Int J 2009;8:539-43. Comprehens Pharm 2011;2:1-3. 28. Dongre VG, Shah SB, Karmuse PP, Phadke M, Jadhav VK. 11. Ilingo K, Shiji Kumar PS. Simultaneous estimation of telmisartan Simultaneous determination of metoprolol succinate and amlodipine and hydrochlorothiazide in pharmaceutical dosage form. Asian J besylate in pharmaceutical dosage form by HPLC. J Pharm Biomed Pharm Health Sci 2011;1:12-5. Anal 2008;46:583-6. 12. Thomas AB, Jagdale SN, Dighe SB, Nanda RK. Simultaneous 29. Rajamanickam V, Rathinaraj BS, Thangavelpandian N, Pandian AR. spectrophotometric estimation of amlodipine besylate and A validated RP-HPLC method of metoprolol Succinate and telmisartan in tablet dosage form. Int J Chem Tech Res 2010;2: amlodipine Succinate from bulk drugs. Scholars Res Library Der 1334-41. Pharmaceutical Methods | July-December 2012 | Vol 3 | Issue 2 110 Patel, et al.: Absorbance correction method of TELM and METO Pharm Lett 2010;2:40-6. 32. ICH Q2 (R1), Harmonizazed Tripatite Guidline, Validation of 30. Rao MM, Rahaman SA, Prasad YR, Reddy PG. RP-HPLC method Analytical Procedure: Text and Methodology, 2005. of Simultaneous estimation of amlodipine Besylate and metoprolol in combined dosage form. Int J Pharm Res Dev-Online 2010; How to cite this article: Patel K, Patel A, Dave J, Patel C. 2:69-72. Absorbance correction method for estimation of telmisartan and 31. Joshi P, Kumar M, Development and validation of a reverse phase metoprolol succinate in combined tablet dosage forms. Pharm HPLC method for the simultaneous estimation of metoprolol and Methods 2012;3:106-11. telmisartan in tablet dosage form. Pelagia Res Library, Der Pharm Source of Support: Nil, Conflict of Interest: None declared. Sinica 2011;2:211-9. Pharmaceutical Methods | July-December 2012 | Vol 3 | Issue 2

Journal

Pharmaceutical MethodsPubmed Central

Published: Aug 1, 168

There are no references for this article.