Spectrophotometric Estimation of Olmesartan Medoxomil and Hydrochlorothiazide in Tablet

Indian Journal of Pharmaceutical Sciences 111 January February 2010 and cardiovascular outcomes in patients with type 2 diabetes and nephropathy. N Engl J Med 2001;345:861-9. 2. Sleight P, Yusuf S, Pogue J. Blood-pressure reduction and cardiovascular risk in the HOPE study. Lancet 2001;358:2130-1. 3. Wright JT Jr, Bakris G, Greene T. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: Results from the AASK trial. J Am Med Assn 2002;288:242131. 4. McCarthy KE, Wang Q, Tsai EW, Gilbert RE, Ip DP, Brooks MA. Determination of losartan and its degradants in COZAAR tablets by reversed-phase high-performance thin-layer chromatography. J Pharm Biomed Anal 1998;17:671-7. 5. Williams RC, Alasandro MS, Fasone VL, Boucher RJ, Edwards JF. Comparison of liquid chromatography, capillary electrophoresis and super-critical fl uid chromatography in the determination of Losartan Potassium drug substance in Cozaar tablets. J Pharm Biomed Anal 1996;14:1539-46. 6. Polinko M, Riffel K, Song H, Lo MW. Simultaneous determination of losartan and EXP3174 in human plasma and urine utilizing liquid chromatography/tandem mass spectrometry. J Pharm Biomed Anal 2003;33:73-84. 7. Furtek CI, Lo MW. Simultaneous determination of a novel angiotensin II receptor blocking agent, losartan, and its metabolite in human plasma and urine by high-performance liquid chromatography. J Pharm Biomed Anal 1997;15:1021-9. 8. Soldner A, Spahn-Langguth H, Mutschler E. HPLC assays to simultaneously determine the angiotensin-AT1 antagonist losartan as well as its main and active metabolite EXP 3174 in biological material of humans and rats. J Pharm Biomed Anal 1998;16:863-73. 9. Yeung PK, Jamieson A, Smith GJ, Fice D, Pollak PT. Determination of plasma concentrations of losartan in patients by HPLC using solid phase extraction and UV detection. Int J Pharm 2000;204:17-22. 10. Iwasa T, Takano T, Hara K, Kamei T. Method for the simultaneous determination of losartan and its major metabolite, EXP-3174, in human plasma by liquid chromatography-electrospray ionization tandem mass spectrometry. J Chromatogr B Biomed Sci Appl 1999;734:325-30. 11. Lastra OC, Lemus IG, Sanchez HJ, Perez RF. Development and validation of an UV derivative spectrophotometric determination of Losartan potassium in tablets. J Pharm Biomed Anal 2003;33:175-80. 12. Ansari M, Kazemipour M, Khosravi F, Baradaran M. A comparative study of fi rst-derivative spectrophotometry and high-performance liquid chromatography applied to the determination of losartan potassium in tablets. Chem Pharm Bull 2004;52:1166-70. 13. Prabhakar AH, Giridhar R. A rapid colorimetric method for the determination of Losartan potassium in bulk and in synthetic mixture for solid dosage form. J Pharm Biomed Anal 2002;27:861-6. 14. Gandhimathi M. HPLC determination of losartan pottassium and ramipril in tablets. Indian drugs 2004;41:120-2.

, degradation product HPLC [2] , HPTLC [3] .One for both OLM and HCT, respectively.This shows regression coeffi cient 0.9999 for OLM at 248.6 nm and 0.9991 for HCT at 272.8 nm.The statistical parameters were calculated.Twenty tablets were weighed accurately and powdered.Powder equivalent to 20 mg of OLM (containing 12.5 mg of HCT) was weighed and transferred to 100 ml volumetric flask and dissolved in 25 ml methanol by shaking the fl ask for 15 min and volume was made up to the mark with 0.1 N NaOH.The solution was filtered through Whatman fi lter paper No. 41.One millilitre aliquot of sample stock solution was transferred to 10 ml volumetric flask and volume was made up to mark with 0.1 N NaOH to get concentration of 20 µg/ml of OLM and 12.5 µg/ml of HCT.The solutions were then scanned over the range of 200 to 360 nm.The spectra were obtained and absorbance was measured at selected wavelengths 260.0 nm (isoabsorptive point) and 272.8 nm for both the drugs.The concentrations of OLM and HCT were calculated by putting the absorbance values in Eqns. 1 and 2.
The accuracy of the proposed method was checked by performing recovery study by addition of standard drug solution to preanalysed tablet sample solution at three different concentration levels (80, 100 and 120%) within the range of linearity for both the drugs.The wavelengths selected for this method should be wavelength (λ max ) one of the component and second one was the isoabsorptive point where the absorptivity of both components was same which is shown in fi g 1. OLM shows maximum absorption at wavelength (λ max ) 248.6 nm, where as the HCT shows  analytical method was developed for determination of HCT and OLM in combination HPLC [4] , The USP described an HPLC method for determination of HCT from tablet formulation [5] .
A double beam, Shimadzu 2450 UV/Vis spectrophotometer connected to a HCL computer loaded with UV Probe 2.21 Software was used in the current investigation.OLM and HCT were supplied by Glenmark Pharmaceutical Ltd and Ajanta Pharmaceuticals Ltd, respectively.Sodium hydroxide and double distilled water were used for this work.A commercial pharmaceutical preparation Olmesar-H of Macleod, Gujarat, India (containing OLM 20 mg and HCT 12.5 mg/tablet) was used for analysis.
Standard stock solution 1.0 mg/ml each of OLM and HCT were prepared in 25 ml 0.1 N NaOH.A further dilution of stock solution was made with 0.1 N NaOH to get a working standard solution of 100 µg/ml of both drugs.Then 10 ml of OLM and 6.25 ml of HCT standard stock solution of each drug was taken in 50 ml volumetric fl ask and diluted with 0.1 N NaOH up to the mark to get 200 µg/ml of OLM and 125 µg/ ml of HCT.This solution used as standard working mixture solution.
From the standard working mixture solution of OLM and HCT, 1 ml of working mixture were taken in 10 ml volumetric fl ask containing 20 µg/ ml of OLM and 12.5 µg/ml of HCT were prepared using 0.1 N NaOH.The standard mixtures prepared were then scanned over the range of UV 200 to 360 nm.The spectra were then obtained and absorbance was measured at selected wavelengths 260.0 nm (isoabsorptive point) and 272.8 nm for both the drugs.The concentrations of OLM and HCT were calculated by inserting the absorbance values in the Eqns.Cx= (Qm-Qy)/(Qx-Qy)×A 1 /ax 1 --( 1) and C Y = (Qm-Qx)/(Qy-Qx)×A 1 /ay 1 -- (2), where Cx and C Y are concentration of OLM and HCT (g/100 ml), respectively, A 1 and A 2 are absorbance of mixture at 248.6 nm and 272.8 nm, respectively, ax 1 and ax 2 denote absorptivity of OLM at 260.0 nm and 272.8 nm, respectively, ay 1 and ay 2 represent absorptivity of HCT at 260.0 nm and 272.8 nm, respectively, Qx and Q Y are ratios of absorptivity of OLM and HCT at 272.8 nm and 260.0 nm, respectively and Qm is the ratio of absorbance of the mixture at 272.6 nm and 260.0 nm.Linearity was constructed in the range 10-30 µg/ml maximum absorption at wavelength (λ max ) 272.8 nm and 260.0 nm is the isoabsorptive point of both drugs.The analytical data for the linearity range shows correlation coefficients of 0.9999 for Olmesartan medoxomil and 0.9991 for HCT at 248.6 nm and 272.8 nm, respectively which is shown in Table 1.For quantitative analysis, concentration of OLM and HCT in tablet sample were determined by using Eqns. 1 and 2, results are shown in Table 2.The detection limits were 0.41 µg/ml for OLM and 0.44 µg/ml for HCT, while quantifi cation limit were 1.25 µg/ml for OLM and 1.33 µg/ml for HCT.The proposed method was validated by performing recovery study.Recovery was in the range of 99.97-100.62% for OLM and HCT respectively, the standard deviation was found to be less than 2%, shows the high precision of the proposed method The method can be used for the routine quality control analysis of the OLM and HCT in combined dosage form.

Fig. 1 :
Fig. 1: Overlay of Spectra of OLM and HCT OLM is olmesartan medoximil and HCT is hydrochlorthiazide and cardiovascular outcomes in patients with type 2 diabetes and nephropathy.N Engl J Med 2001;345:861-9.2. Sleight P, Yusuf S, Pogue J. Blood-pressure reduction and cardiovascular risk in the HOPE study.Lancet 2001;358:2130-1.3. Wright JT Jr, Bakris G, Greene T. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: Results from the AASK trial.J Am Med Assn 2002;288:2421-31.4. McCarthy KE, Wang Q, Tsai EW, Gilbert RE, Ip DP, Brooks MA.Kazemipour M, Khosravi F, Baradaran M. A comparative study of fi rst-derivative spectrophotometry and high-performance liquid chromatography applied to the determination of losartan potassium in tablets.Chem Pharm Bull 2004;52:1166-70.13.Prabhakar AH, Giridhar R. A rapid colorimetric method for the determination of Losartan potassium in bulk and in synthetic mixture for solid dosage form.J Pharm Biomed Anal 2002;27:861-6.14.Gandhimathi M. HPLC determination of losartan pottassium and ramipril in tablets.Indian drugs 2004;41:120-2.
survey revealed that OLM is not yet offi cial in any pharmacopoeia.Several analytical methods have been reported for the determination of olmesartan medoxomil in biological fluids includes LC-MS-MS

TABLE 2 : RESULTS OF COMMERCIAL TABLET FORMULATION ANALYSIS
*average of 5 determinants