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SHORT COMMUNICATION
Year : 2007  |  Volume : 69  |  Issue : 6  |  Page : 844-846
Simultaneous spectrophotometric estimation of metformin and repaglinide in a synthetic mixture


1 Department of Pharmaceutical Chemistry, S. K. Patel College of Pharmaceutical Education and Research, Ganpat Vidyanagar, Mehsana - 382 711, India
2 Department of Pharmaceutical Chemistry, L. M. College of Pharmacy, Navrangpura, Ahmedabad - 380 009, India

Date of Submission05-Dec-2005
Date of Decision13-Jul-2007
Date of Acceptance23-Dec-2007

Correspondence Address:
J R Patel
Department of Pharmaceutical Chemistry, S. K. Patel College of Pharmaceutical Education and Research, Ganpat Vidyanagar, Mehsana - 382 711
India
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DOI: 10.4103/0250-474X.39451

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   Abstract 

Two simple, rapid, accurate and economical methods have been developed for the simultaneous estimation of metformin and repaglinide in the synthetic mixture. The linearity was observed in the concentration range of 4-24 g/ml for the both metformin and repaglinide. First method is based on the simultaneous equations, absorbances of both the drugs were determined at 240 nm (λ max of metformin) and at 291.5 nm (λ max of repaglinide). Metformin does not show any absorbance at 291.5 nm, hence its absorptivity was taken zero in the calculation. The method was validated in terms of accuracy (99.240.99, 100.980.89) and precision (intra-day variations 0.58-1.21, 2.12-3.12 and inter-day variations 0.62-1.42, 2.20-3.08). Second method is based on Q-absorbance ratio; absorbances of both the drugs were determined at 240 nm (l max of metformin) and at isoabsorptive point (254.8 nm). Q-absorption ratio method was validated in terms of accuracy (98.571.05, 98.621.2402) and precision (intra-day variations 0.58-1.21, 1.01-3.53 and inter-day variations 0.62-1.42, 1.15-3.74). The proposed methods were found accurate, reproducible and economical for the routine analysis of both the drugs in the synthetic mixture.


Keywords: Metformin, repaglinide, spectrophotometric analysis


How to cite this article:
Patel J R, Suhagia B N, Patel B H. Simultaneous spectrophotometric estimation of metformin and repaglinide in a synthetic mixture. Indian J Pharm Sci 2007;69:844-6

How to cite this URL:
Patel J R, Suhagia B N, Patel B H. Simultaneous spectrophotometric estimation of metformin and repaglinide in a synthetic mixture. Indian J Pharm Sci [serial online] 2007 [cited 2014 Sep 19];69:844-6. Available from: http://www.ijpsonline.com/text.asp?2007/69/6/844/39451


Metformin Hydrochloride (MET) is a biguanide class of antidiabetic drug, chemically is N,N-dimethylimidodicarbonimidic diamide hydro-chloride [1],[3],[4],[5],[6],[7],[8],[9],[10],[11],[12]. Repaglinide (REPA) is a meglitinide antidiabetic used for the treatment of type 2 diabetes mellitus, chemically is (+)-2-ethoxy-α-{[(S)-α-isobutyl-o -piperidinobenzyl]carbamoyl}- p -toluicacid [2],[13],[14],[15] .

Shimadzu model 1601 double beam UV/Vis spectrophotometer with a pair of 10 mm matched quartz cells was used to measure absorbance of the resulting solutions. Sartorius CP224S analytical balance, an ultrasonicater (Frontline FS 4). MET and REPA were obtained from Restech Pharmaceutical, Ahmedabad and absolute alcohol from S. D. Fine Chemicals, Mumbai.

Standard MET and REPA stock solution of 100g/ml concentration was prepared in absolute alcohol. The synthetic mixture of MET and REPA was prepared in the ratio of 1:1. MET and REPA powder (5 mg each) was accurately weighed and transferred to 50 ml volumetric flask. The content was mixed with 40 ml alcohol. Common excipients, which are used in the tablet formulation, were added in this mixture and sonicated for 20 min. This solution was filtered through the Whatman filter paper No. 41 and the residue was washed thoroughly with alcohol. The filtrate and washings were combined and diluted to the 50 ml with alcohol to get solution having MET (100 g/ml) and REPA (100 g/ml).

The standard stock solutions of MET and REPA were scanned in the range of 200 nm to 400 nm against absolute alcohol as a blank. Maximum absorbance was obtained at 240 nm and 291.5 nm for MET and REPA, respectively. Iso-absorptive point was found at 254.8 nm. A calibration curve was plotted over a concentration range 4-24 g/ml for both MET and REPA. Absorbance of each solution was measured at both the wavelength 240 nm and 291.5 nm. Calibration curves were constructed for MET and REPA by plotting absorbance versus concentrations at both wavelengths. Each reading was average of three determinations. Absorbance of each solution was measured at the three wavelengths 240 nm, 291.5 nm and 254.8 nm. Calibration curves were constructed for MET and REPA by plotting absorbance versus concentrations at three wavelengths. Each reading was average of three determinations.

Accuracy was determined in term of percent recovery. The proposed method was applied to determine MET and REPA in the synthetic mixture. The recovery experiments were carried out in triplicate by spiking previously analyzed samples of the synthetic mixture with three different concentrations of standards. Precision was determined in term of intra-day and inter-day precision. The absorbance of final sample solution was measured against absolute alcohol as a blank at 240, 291.5 and 254.8 nm. The amount of MET and REPA were calculated using simultaneous equations as well as Q-absorbance ratio method.

Calibration curves for MET and REPA over concentration range of 4-24 g/ml were plotted and molar absorptivity for both the compounds were calculated at three wavelengths 240 nm ('λ max of MET), 254.8 nm (Isoabsorptive point) and 291.5 nm ('λ max of REPA). MET did not show any absorbance at 291.5 nm, hence absorptivity of MET was taken zero in the calculation. The linearity of the calibration graphs was validated by the high value of correlation coefficients of the regression [Table - 1]. The criteria for obtaining maximum precision [1] , by simultaneous equations method, were calculated and found to be out side the range 0.1-2.0.

LOD for MET and REPA were found to be 0.38 g/ml and 0.69 g/ml, respectively while LOQ for MET and REPA were found to be 1.15 g/ml and 2.08 g/ml respectively by both the methods. These data show that both the methods are sensitive for the determination of MET and REPA.

The percent recoveries obtained were 99.24 to 101.23 and 100.98 to 101.08 for MET and REPA, respectively by simultaneous equation method; 98.05 to 99.05 and 98.62 to 99.12 for MET and REPA, respectively by Q-absorbance ratio method. The low value of SD indicates that both the methods are accurate. The low % CV values of intra-day and inter-day variations reveal that the proposed methods are robust [Table - 1].

In the simultaneous equation method concentration of MET and REPA in the synthetic mixture were found out by solving following equations; C m = (A 2 a r1 -A 1 a r2 )/(a m2 a r1 -a m1 a r2 ) and C r = (A 1 a m2 - A 2 a m1 )/(a m2 a r1 -a m1 a r2 ), where; C m , C r = concentration of MET and REPA in the sample solution, A 1 , A 2 = absorbances of the sample solution at 240 nm and 291.5 nm, respectively, a m1 and a m2 = molar absorptivities of MET at 240 nm and 291.5 nm, respectively and a r1 and a r2 = molar absorptivities of REPA at 240 nm and 291.5 nm, respectively

In the Q- absorbance ratio method concentration of MET and REPA in the sample solutions were calculated using equations C m2 = (Q o -Q r /Q m -Q r )A 3 /a m3 and C p2 = A 3 /a r3 -C m2 , where A 1 and A 3 are absorbances of sample solution at 240 nm and 254.8 nm; and a m3 and a r3 are molar absorptivity of MET and REPA at 254.8 nm; a m1 and a r1 are molar absorptivity of MET and REPA at 240 nm. Q o =A 1 /A 3 , Q m =a m1 /a m3 and Q r =a r1 /a r3 .

The proposed validated methods were successfully applied to determine MET and REPA in the synthetic mixture. The % recoveries for MET and REPA obtained were 101.561.20, 101.001.53 by simultaneous equations method and 98.011.58, 98.151.63 by Q-absorption ratio method respectively. No interference of the excipients with the absorbance appeared; hence the proposed methods are applicable for the quantitative determination of MET and REPA in synthetic mixture.

 
   References Top

1.Budavari S, editor. The Merck Index. 13th ed. Whitehouse station, (NJ, USA): Merck and Co; 2001. p. 790.  Back to cited text no. 1    
2.Budavari S, editor. The Merck Index. 13th ed. Whitehouse station, (NJ, USA): Merck and Co; 2001. p. 1458.  Back to cited text no. 2    
3.Song-Jin T, Jing-Zheng S, Hai-Feng C, Zeng-Pei S. Determination of Metformin in plasma by capillary electrophoresis using field amplified sample stacking technique. J Chromatogr B 1998;708:277-81.  Back to cited text no. 3    
4.Ojala-Karlsoon P, Rouru J, Koulu M. Determination of Metformin in plsam by high performance liquid chromatography. J Chromatotgr A 1992;583:270-5.  Back to cited text no. 4    
5.Ross MS. Dried blood spot liquid chromatography assay for therapeutic drug monitering of Metformin. J Chromatogr A 1977;133:408-10.  Back to cited text no. 5    
6.Aburuz S, Millership J, McElnay J. The development and validation of liquid chromatography method for simultaneous determination of Metformin and glipizide, gliclazide, glibenclamide in plasma. J Chromatogr B 2005;817:277-82.  Back to cited text no. 6    
7.Koseki N, Kawashita H, Niina M, Nagae Y, Masuda N. Development and validation for high selective quantitative determination of metformine in human plasma by cation exchanging with normal phase LC/MS/MS. Pharm Biomed Anal 2005;36:1063-6.  Back to cited text no. 7    
8.Wang Y, Tang Y, Gu J, Fawcett JP, Bai X. Rapid and sensitive liquid chromatography-tandem mass spectrometric method for quantitation of Metformin in human plasma. J Chromatogr B 2004;808:215-9.  Back to cited text no. 8    
9.Kolte BL, Raut BB, Deo AA, Bagool MA Shinde DB, Simultaneous high performance liquid chromatographic determination of Pioglitazone and Metformin in pharmaceutical dosage form. J Chromatogr Sci 2004;42:27-30.  Back to cited text no. 9    
10.Zhang M, Moore GA, Lever M, Gardiner SJ, Kirkpatrick CM, Begg EJ. Rapid and simple high performance liquid chromatographic assay for the determination of Metformin in human plasma and breast milk. Pharm Biomed Anal 2001;25:77-82.  Back to cited text no. 10    
11.Gandhimathi M, Anandakumar K, Cheriyan A, Ravi TK. Simultaneous estimation of Metformin and gliclazide in tablet using reverse phase high performance liquid chromatography. Indian J Pharm Sci 2003;65:530-4.  Back to cited text no. 11    
12.Jain AK, Agrawal RK. Simultaneous estimation of Gliclazide and Metformin hydrochloride in combined dosage forms. Indian J Pharm ci 2002;64:88-91.  Back to cited text no. 12    
13.Gandhimathi M, Ravi TK, Renu SK. Determination of Repaglinide in pharmaceutical formulation by HPLC with UV detection. Anal Sci 2003;9:1675-8.  Back to cited text no. 13    
14.Reddy KV, Babu JM, Mathad VT, Eswaraiah S, Reddy MS, Dubey PK, et al. Impurity profile study of Repaglinide. J Pharm Biomed Anal 2003;32:461-5.  Back to cited text no. 14  [PUBMED]  
15.Jain SK, Agrawal GP, Jain NK. Spectrophotometric determination of Repaglinide in tablet dosage form. Indian J Pharm Sci 2005;67:249-51.  Back to cited text no. 15    



 
 
    Tables

  [Table - 1]

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