Novel 2-pyrazoline derivatives as potential antibacterial and antifungal agents

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(1)www.ijpsonline.com. Indian Journal of Pharmaceutical Sciences Scientific Publication of the Indian Pharmaceutical Association Indexed in Ind MED, EMBASE/Excerpta Medica, International Pharmaceutical Abstracts, Chemical Abstracts.. Volume 70. Number 1. January-February 2008. CONTENTS. REVIEW ARTICLES. R. S. KADAM AND K. R. IYER. A Decision Tree for Rapid Quality Assurance and Control of Rifampicin-Containing Oral Dosage Forms for Global Distribution for Tuberculosis Treatment Y. ASHOKRAJ, SHRUTIDEVI AGRAWAL AND R. PANCHAGNULA. K. N. VENUGOPALA AND B. S. JAYASHREE 1-4. Transdermal Delivery by Iontophoresis 5-10. RESEARCH PAPERS In vivo Evaluation of Single Dose Tetanus Toxoid Vaccine Formulation with Chitosan Microspheres R. MANIVANNAN, S. A. DHANARAJ, Y. UDAYA BHASKARA RAO, A. BALASUBRAMANIAM, N. L. GOWRISHANKAR, N. JAWAHAR AND S. JUBIE. 94-96. HPLC Estimation of berberine in Tinospora cordifolia and Tinospora sinensis 11-15. G. V. SRINIVASAN, K. P. UNNIKRISHNAN, A. B. REMA SHREE AND INDIRA BALACHANDRAN. 96-99. Parenteral Formulation of Zopiclone 16-21. Design and Optimization of Diclofenac Sodium Controlled Release Solid Dispersions by Response Surface Methodology. P. V. SWAMY, P. SUSHMA, G. CHIRAG, K. PRASAD, M. YOUNUS ALI AND S. A. RAJU. 99-102. Simultaneous Spectrophotometric Determination of Lansoprazole and Domperidone in Capsule Dosage Form. H. N. SHIVAKUMAR, B. G. DESAI AND G. DESHMUKH. 22-30. Evaluation of Free Radical Scavenging Activity of an Ayurvedic Formulation, Panchvalkala. A. P. SHERJE, A. V. KASTURE, K. N. GUJAR AND P. G. YEOLE. 31-35. Validation of Different Methods of Preparation of Adhatoda vasica Leaf Juice by QuantiÞcation of Total Alkaloids and Vasicine S. SONI, SHEETAL ANANDJIWALA, G. PATEL AND M. RAJANI. Formulation and Characterization of Mucoadhesive Buccal Films of Glipizide MONA SEMALTY, A. SEMALTY AND G. KUMAR. 43-48. Synthesis, Antimicrobial and Anti-inßammatory Activity of 2,5-Disubstituted-1,3,4-oxadiazoles G. NAGALAKSHMI. ASMITA GAJBHIYE, V. MALLAREDDY AND G. ACHAIAH. 61-65. P. D. NAKHAT, A. A. KONDAWAR, L. G. RATHI AND P. G. YEOLE 121-124. 66-70. S. L. BALDANIA, K. K. BHATT, R. S. MEHTA, D. A. SHAH AND TEJAL R. GANDHI. Optimization of Fast Dissolving Etoricoxib Tablets Prepared by Sublimation Technique D. M. PATEL AND M. M. PATEL. SHORT COMMUNICATIONS Isolation of Liver Aldehyde Oxidase Containing Fractions from Different Animals and Determination of Kinetic Parameters for Benzaldehyde. 114-117. Synthesis and Pharmacological Evaluation of (6-Substituted 4-Oxo-4H-chromene-3 yl) methyl N-substituted Aminoacetates 118-120. Development and In Vitro Evaluation of Buccoadhesive Tablets of Metoprolol Tartrate RP-HPLC Estimation of Venlafaxine Hydrochloride in Tablet Dosage Forms. 71-76. Simultaneous Estimation of Esomeprazole and Domperidone by UV Spectrophotometric Method. 77-84. In Vitro Anthelmintic Activity of Baliospermum montanum Muell. Arg roots. Furosemide-loaded Alginate Microspheres Prepared by Ionic Cross-linking Technique: Morphology and Release Characteristics M. K. DAS AND P. C. SENAPATI. 111-113. Effect of Some Clinically Used Proteolytic Enzymes on Inßammation in Rats. 56-60. Development and Evaluation of a Chloramphenicol Hypertonic Ophthalmic Solution A. V. JITHAN, C. KRISHNA MOHAN, AND M. VIMALADEVI. V. RAVI, T. M. PRAMOD KUMAR AND SIDDARAMAIAH. A. H. M. VISWANATHA SWAMY AND P A. PATIL. Design and In Vitro Characterization of Buccoadhesive Drug Delivery System of Insulin J. SAHNI, S. RAJ, F. J. AHMAD AND R. K. KHAR. 108-111. Novel Colon Targeted Drug Delivery System Using Natural Polymers. 49-55. Ascorbic Acid Inhibits Development of Tolerance and Dependence to Opiates in Mice: Possible Glutamatergic or Dopaminergic Modulation S. K. KULKARNI, C. DESHPANDE AND A. DHIR. 105-108. Spectrophotometric Estimation of Ethamsylate and Mefenamic Acid from a Binary Mixture by Dual Wavelength and Simultaneous Equation Methods ANJU GOYAL AND I. SINGHVI. 36-42. 102-105. Novel 2-Pyrazoline Derivatives as Potential Antibacterial and Antifungal Agents SUVARNA KINI AND A. M. GANDHI. SHEETAL ANANDJIWALA, M. S. BAGUL, M. PARABIA AND M. RAJANI. January - February 2008. 91-94. Physicochemical and Pharmacokinetic Parameters in Drug Selection and Loading for Transdermal Drug Delivery N. S. CHANDRASHEKAR AND R. H. SHOBHA RANI. Ionic Cross-linked Chitosan Beads for Extended Release of Ciproßoxacin: In vitro Characterization A. SRINATHA, J. K. PANDIT AND S. SINGH. 88-91. In vitro Antiviral Activity of some Novel Isatin Derivatives against HCV and SARS-CoV Viruses P. SELVAM, N. MURGESH, M. CHANDRAMOHAN, E. DE CLERCQ, E. KEYAERTS, L. VIJGEN, P. MAES, J. NEYTS AND M. V. RANST. SWATI RAWAT, SUDHA VENGURLEKAR, B. RAKESH, S. JAIN, G. SRIKARTI. 85-88. Microwave-Induced Synthesis of Schiff Bases of Aminothiazolyl Bromocoumarins as Antibacterials. S. LAKSHMANA PRABU, A. SHIRWAIKAR, ANNIE SHIRWAIKAR, C. DINESH KUMAR, A. JOSEPH AND R. KUMAR. R. G. MALI AND R. R. WADEKAR. 124-128. 128-131. 131-133. REFEREES FOR INDIAN JOURNAL OF PHARMCEUTICAL SCIENCES DURING 2006 & 2007 134-134. Indian Journal of Pharmaceutical Sciences i. 135.

(2) www.ijpsonline.com. DOM in marketed capsule formulation. The assay values were in good agreement with the corresponding labeled claim. The recovery studies show accuracy of the method. On observing the validation parameters both the methods were found to be accurate, precise and speciÞc. Hence the methods can be employed for quality control and routine analysis of lansoprazole and domperidone in pharmaceutical formulations.. 7.. 8. 9.. ACKNOWLEDGEMENTS The authors thank Dr. Reddy’s Laboratories Ltd., Medak (A.P.) and Aurobindo Pharma Ltd., Hyderabad for providing the gift samples of lansoprazole and domperidone respectively. Authors are also thankful to Institute of Pharmaceutical Education and Research, Wardha for providing necessary facilities for the research work.. 10. 11. 12. 13.. 14.. REFERENCES 1. 2. 3. 4.. 5. 6.. Sweetman SC, editors. Martindale-The Complete Drug Reference. 34th ed. London: Pharmaceutical Press; 2005. p. 1269-70. USP 28- NF 23. Asian Edition. Rockville, MD: United States Pharmacopeial Convention, Inc;,. 2005. p. 1110. Keith GT. Gastrointestinal and liver drugs. In: Gennaro AR, editors. Remington: The Science and Practice of Pharmacy. 20th ed. Vol. I. Maryland: Lippincott Williams and Wilkins; 2000. p. 1226. Unoa T, Yasui FN, Takahata T, Sugawara K, Tateishi T. determination of lansoparazole and two of its metabolites by liquid-liquid extraction and automated column-witching high-performance liquid chromatography: Application to measuring CYP2C19 activity. J Chromatogr B Anal Technol Biomed Life Sci 2005;816:309. Avgerinos A, Karidas T, Potsides C, Axarlis S. Determination of lansoprazole in biological ßuids and pharmaceutical dosage by HPLC. Eur J Drug Metab Pharmacokinet 1998;23:329. Pandya KK, Mody VD, Satia MC, Mody A, Mody RK, Chakravarthy BK,. 15. 16. 17.. et al. High performance thin layer chromatographic method for detection and determination of lansoprazole in human plasma and its use in pharmacokinetic studies. J Chromotoqr B Biomed Sci Appl 1997;693:199. Celso H, Oliveiraa R, Barrientos-Astagarragab E, Eduardo A, Gustavo D, Mendesb D, et al. Lansoprazole quantitation in human plasma by liquid chromatography-electrospray tandem mass spectrometry. J Chromatogr B 2003;783:453. Puratchikodi A, Krishnamoorthy G, Joykat B, Valarmathy R. Spectrometric method for the determination of lansoprazole. Eastern Pharmacist 1996;43:446. Wahbi AA, Omatna AR, Azzig A, Hada M, Matwa SM. Spectrometric determination of omeprazole, lansoprazole and pantoprazole in pharmaceutical formulations. J Pharm Biomed Anal 2002;30:1133. Altman DF. In: Katzung BG. editor. Basic and clinical Pharmacology. 8th ed. Delhi: Mc-Graw Hill Publishing Division; 2001. p. 1067. British Pharmacopoeia, Addendum: British pharmacopoeia Commission ofÞce; 1996. p. 1767. European Pharmacopoeia, 5th ed. Vol. II. Strasbourg: Council of Europe; 1997. p. 779. Smit MJ, Sutherland FC, Hundt HK, Swart KJ, Hundt AF. Rapid and sensitive liquid chromatography-tandem mass spectrometry method for the quantitation of domperidone in human plasma. J Chromatogr A 2002;949:65. Vinodhlni C, Vaidhyalingam V, Ajithadas A, Niraimathi, Shantha A. Simultaneous estimation of cinarizine and domperidone in solid oral dosage form using Spectrophotometric method. Indian Drugs 2002;39:491. Manoj K, Anbazhagan S. Reverse phase high performance liquid chromatographic method for simultaneous estimation of domperidone and pantoprazole from tablet formulation. Indian Drugs 2004;41:604. USP 28- NF 23. Asian Edition. Rockville, MD: United States Pharmacopeial Convention, Inc.;. 2005. p. 2748-9. Davidson AG. Ultraviolet-visible absorption spectrophotometry. In: Beckett AH, Stenlake JB, Editors. Practical Pharmaceutical Chemistry. 4th ed. Part II. New Delhi: CBS Publishers and Distributors; 2004. p. 286-8. Accepted 2 February 2008 Revised 2 August 2007 Received 16 December 2006 Indian J. Pharm. Sci., 2008, 70 (1): 102-105. Novel 2-Pyrazoline Derivatives as Potential Antibacterial and Antifungal Agents SUVARNA KINI* AND A. M. GANDHI Department of Pharmaceutical Chemistry, Manipal College of Pharmaceutical Sciences, Manipal - 576 104, India. Kini, et al.: 2-Pyrazoline Derivatives as Antibacterial and Antifungal Agents The 1,3,5-trisubstituted-2-pyrazolines were synthesized by refluxing isoniazid with various substituted diarylchalcones in N,N-dimethylformamide at 120-140°. The physical and spectral data such as M.P., Rf, elemental analysis, IR, *For correspondence E-mail: suvarna.gk@manipal.edu January - February 2008. Indian Journal of Pharmaceutical Sciences. 105.

(3) www.ijpsonline.com. NMR and Mass was obtained for the synthesized compounds and the structures were confirmed. The screening of the synthesized compounds for antimicrobial activity was performed against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli and Aspergillus niger. Key words: Pyrazolines, antibacterial agents, antifungal agents. 2-pyrazolines are reported as antibacterial1, antifungal2-4, antimicrobial 5 , antiviral 6 , anti-arthritis 7 and antiinflammatory 7,8 agents. Encouraged by these facts, we selected to work on 1,3,5-trisubstituted-2pyrazolines with different substitutions on the phenyl ring. The antibacterial activity and antifungal activity was screened by cup-plate agar diffusion method and the zone of inhibition for each microorganism at different concentrations of the compounds was measured. Melting points of the compounds were determined on a Toshniwal ScientiÞc melting point apparatus and are uncorrected. Purity of the compounds was checked by Thin Layer Chromatography using precoated Merck Silica gel GF 254 micro TLC plates and spots were detected under UV. UV spectra were recorded on UV/ Vis spectrophotometer (Shimadzu), UV-1601 PC, IR spectra were recorded in KBr disc on a FTIR_8300, KBr Press (Shimadzu) spectrophotometer at Manipal College Of Pharmaceutical Sciences, Manipal. 1H NMR spectra (DMSO-d 6 ) were obtained using Varian 300 MHz Mercury NMR spectrometer from Shimadzu Analytical Technique Center, Department of Chemistry, Pune University, Pune. Mass spectra of the synthesized compounds were obtained using Mass Spectrometer, Shimadzu QP5050 from Shimadzu Analytical Technique Center, Department of Chemistry, Pune University, Pune. Chemicals were obtained from S.D. Fine Chemicals Ltd dealers from Mangalore. Synthesis of 1,3,5-trisubstituted-2-pyrazolines [compound P13 (5-(4-ßuorophenyl)-3-(4-ßuorophenyl)1-isonicotinoyl-pyrazoline)] 9,10 was performed by taking equimolar quantities (0.02 mol) of 4-fluoro benzaldehyde and 4-ßuoro acetophenone in a 250 ml conical flask and dissolving in minimum amount of 95% ethanol. The mixture was then cooled and 8 ml of 10% potassium hydroxide solution was added. The mixture was stirred over a magnetic stirrer for a period of 24 h and left in an ice chest overnight. On the next day, the mixture was poured into a beaker containing ice-cold water. Then the aqueous layer was acidified with conc. HCl. The precipitated chalcone (1-(4-ßuorophenyl)-3-(4-ßuorophenyl)-2-propen-1-one) 106. was Þltered at pump and recrystallized from aqueous methanol. IR (KBr)cm-1:1598.9 (C = C), 1660.6 (C = O), 3072.4 (C-H). (1-(4-ßuorophenyl)-3-(4-ßuorophenyl)2-propen-1-one) (0.05 mol) was added to isoniazid (0.1 mol) in a 100 ml R.B.F. containing 30 ml of N, N-dimethylformamide. The mixture was refluxed at 120° to 140° for a period of 8-10 h. After cooling, the reaction mixture was poured into a beaker containing ice-cold water and the product separated was scooped off and dried over a clean Þlter paper. The pyrazoline obtained was recrystallized using benzene-petroleum ether. Single spot on TLC established the purity of the compound. Solvent system used was Hexane: ethyl O. O. R1 C. R2 +. H. C. CH3. Substituted acetophenone. Substituted benzaldehyde. 10% KOH Ethanol. R2. R1 CH. CH. C. (CH 01-15) 01-21) O (CH C. N. NHNH2. DMF. O. R1. R2 N C. N O. N. ((P P 01-21 ) 01-15) Fig. 1: Scheme for pyrazoline synthesis. Where, R1 = -H, -Cl(m), -Cl(p), -F(p), -OCH3(p), -OCH3(m, p), N(CH3)2(p), -NO2(m) R2 = -F(p), -Cl(p), -Br(p), -OCH3(p).. Indian Journal of Pharmaceutical Sciences. January - February 2008.

(4) www.ijpsonline.com. acetate in 4:1 ratio. IR (KBr)cm-1: 1641.3 (N-C = O), 1595.0 (C = N), 1215.1 (C-N), 2914.2 (C-H,CH2),1H NMR (δ values) ppm: aromatic hydrogens 6.7-8.6 δ (m, 12H,Ar-H), CH2 methylene 3.4 δ (s, 2H, CH2), CH methine 5.6 δ (d, 1H,CH-Ar). The other derivatives were prepared in a similar way with different substituted chalcones according to the scheme of synthesis given in Þg.1. The physical data of the synthesized compounds is given in Table 1. All the synthesized compounds were screened in vitro for antibacterial activity against Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli at the concentrations 200, 300, 400 and 500 mg/ml and for antifungal activity against Aspergillus niger at 100, 200, 300, 400 µg/ml by cup-plate agar diffusion method11. The concentrations used in screening were chosen after determining the MICs of each compound. The solvent used was. dimethylsulfoxide (DMSO) further diluted with water. Muller Hinton agar was used as the growth medium for the bacterial species and Sabouraud’s agar was the growth medium for the fungal species. DMSO was used as a control for all the type of microorganisms. The control showed no activity against the strains of microorganisms used. Antimicrobial activity and antifungal activity was measured as a function of diameter of zone of inhibition (mm). The results were compared with standard drugs ciproßoxacin for antibacterial activity and ßuconazole for antifungal activity by measuring the zone of inhibition in mm at 200 and 100 μg/ml respectively. At 200 μg/ml, compounds P14 and P15 were found most effective of the synthesized compounds against S. aureus, (zone of inhibition 15 mm) and compound P14 is the most effective among the synthesized compounds at 200 μg/ml against B. subtilis, (zone of inhibition 16 mm). Compounds P02, P08, P09, P10, P11 were the most. TABLE 1: PHYSICAL DATA OF THE SYNTHESIZED PYRAZOLINES Pyrazoline P01 P02 P03 P04 P05 P06 P07 P08 P09 P10 P11 P12 P13 P14 P15. R1 -F (p) -Cl (m) -OCH3 (p) -N(CH3)2 (p) -Cl (p) -OCH3 (m,p) -N(CH3)2 (p) -Cl (p) -NO2 (m) -OCH3 (m,p) -F (p) -N(CH3)2 (p) -F (p) -Cl (p) -OCH3 (p). R2 -Cl (p) -Cl (p) -Cl (p) -Cl (p) -Cl (p) -Cl (p) -OCH3 (p) -OCH3 (p) -OCH3 (p) -OCH3 (p) -Br (p) -Br (p) -F (p) -F (p) -F (p). Rf Value 0.73 0.64 0.77 0.11 0.17 0.11 0.17 0.16 0.31 0.30 0.15 0.14 0.19 0.15 0.12. m.p. (°) 132-133 123-125 172-174 163-165 86-88 166-167 188-190 214-215 170-172 188-189 111-113 96-98 112-114 162-163 157-158. % Yield 51 55 58 49 34 50 52 59 36 47 53 32 44 65 58. All the compounds gave satisfactory spectral and elemental data. TABLE 2: RESULTS OF IN VITRO ANTIBACTERIAL AND ANTIFUNGAL ACTIVITY Code P01 P02 P03 P04 P05 P06 P07 P08 P09 P10 P11 P12 P13 P14 P15. S. aureus B 12 14 13 13 12 12 12 12 13 12 12 12 15 15. C 13 16 14 14 14 13 13 14 15 13 14 13 17 17. D 15 18 15 15 16 14 15 16 17 14 15 14 19 18. B. subtilis E 16 22 17 17 17 16 13 16 18 20 16 17 15 21 20. B 13 13 14 12 12 12 12 12 12 16 14. C 14 14 16 13 13 13 14 12 13 14 18 15. D 16 15 17 15 16 14 14 15 14 15 12 16 20 16. E. coli E 17 17 19 16 19 15 16 17 16 16 14 19 22 18. B 12 15 12 12 13 12 12 15 15 15 15 12 12 14 12. C 13 17 14 13 14 13 13 18 16 17 17 14 13 16 13. D 14 19 16 14 16 14 14 21 17 19 21 15 16 18 14. P. aeruginosa E 16 21 17 16 17 15 16 23 19 21 23 17 18 20 16. B 15 18 21 20 15 12 18 17 17 13 16 -. C 16 20 24 22 19 16 21 19 20 15 18 -. D 18 22 26 23 22 20 24 22 23 17 20 -. A. niger E 20 26 28 25 25 23 26 24 25 20 23 -. A 12 12 14 19 20 16 15 15 16 -. B 13 13 15 21 22 18 17 16 18 -. C 14 15 16 23 24 20 19 18 20 -. D 16 16 18 24 26 22 20 19 22 -. A, B, C, D, E indicates concentration of compounds at 100 μg/ml, 200 μg/ml, 300 μg/ml, 400 μg/ml and 500 μg/ml, respectively. Ciproßoxacin (200 μg/ml) had 26 mm zone of inhibition for S. aureus, 25 mm for B. subtilis, 26 mm for E. coli, 30 mm for P. aeruginosa microorganisms respectively and ßuconazole (100 μg/ml ) had 28 mm zone of inhibition for A. niger organism. Figures indicate diameter of the zone of inhibition in mm including the diameter of cup (i.e. 10 mm). ‘-’ indicates resistance.. January - February 2008. Indian Journal of Pharmaceutical Sciences. 107.

(5) www.ijpsonline.com. effective among the synthesized compounds against E. coli, (zone of inhibition 15 mm) and compound P05 was the most effective at 200 μg/ml among the synthesized compounds against P. aeruginosa, ( zone of inhibition 21 mm). At 100 μg/ml the maximum diameter of zone of inhibition (20 mm) against Aspergillus niger was observed for compound P08; indicating that, it is the most effective among the synthesized compounds against Aspergillus niger. The results of the antibacterial and antifungal activity are given in Table 2.. ACKNOWLEDGMENTS The authors are grateful to Shimadzu Analytical Technique Center, Dept. of Chemistry, Pune University, Pune for providing the spectral details in time.. REFERENCES 1. 2.. 3.. Mittra AS, Rao S. Synthesis and Fungicidal activity of some 2,4disubstituted thiazoles. Indian J Chem 1977;15:1062-3. 4. Rich S, Horsfall JG. Fungitoxicity of heterocyclic nitrogen compounds. Chem Abst 1952;46:11543. 5. Shah M, Patel P, Korgaokar S, Parekh H. Synthesis of pyrazolines, isoxazoles and cynopyridines as potential antimicrobial agents. Indian J Chem 1996;35:1282-4. 6. Husain MI, Shukla S. Synthesis and Biological activity of 4-(3-Aryl4-oxo-2-thioxothiazolidin-5-ylimino)-3-methyl-1-(N,N-disubstituted amino-methyl)pyrazolin-5-ones. Indian J Chem 1986;25:983-6. 7. Rangari V, Gupta VN, Atal CK. Synthesis, anti-inflammatory and anti-arthritic activity of newer beta-boswellic acid derivatives. Indian J Pharm Sci 1990;52:158-60. 8. Nugent AR, Murphy M, Schlachter TS, Dunn CJ, Smith RJ, Staite ND, et al. Pyrazoline Bisphosphonate esters as novel anti-inßammatory and antiarthritic agents. J Med Chem 1993;36:134-8. 9. Dhar DN. The Chemistry of Chalcones and Related Compounds. New York: Wiley Interscience; 1981. p. 213. 10. Ahmed M, Singh, B, Ranjana Sharma, Talesara GL. Synthesis of 1-(NAlkoxyphthalimido)-3,5-diaryl-2-pyrazolines. Indian J Heterocycl Chem 2004;14:23-5. 11. Collee JG, Miles RS, Watt B. Laboratory control of antimicrobial therapy. In: Collee JG, Fraser AG, Marmion BP, Simmons A, editors. Mackie and McCartney Practical Medical Microbiology, 14th ed. New York: Churchill Livingstone; 1996. p. 151-78.. Fahmy AM, Hassa KM, Khalaf AA, Ahmed, RA. Synthesis of some new beta-lactams, 4-thiazolidinones and pyrazolines. Indian J Chem 1987;26:884-7. Das NB, Mittra AS. Fungicides derived from 2-pyrazolin-5-ones. Indian J Chem 1978;16:638-40.. Accepted 2 February 2008 Revised 4 August 2007 Received 29 May 2006 Indian J. Pharm. Sci., 2008, 70 (1): 105-108. Spectrophotometric Estimation of Ethamsylate and Mefenamic Acid from a Binary Mixture by Dual Wavelength and Simultaneous Equation Methods ANJU GOYAL* AND I. SINGHVI1 Department of Pharmaceutical Chemistry, B. N. P. G. College of Pharmacy, Udaipur - 313 002, 1Department of Pharmaceutical Sciences, M. L. Sukhadia University, Udaipur - 313 001, India. Goyal, et al.: Simultaneous Analysis of Ethamsylate and Mefenamic Acid Two simple, accurate, economical and reproducible spectrophotometric methods for simultaneous estimation of twocomponent drug mixture of ethamsylate and mefenamic acid in combined tablet dosage form have been developed. The first developed method involves formation and solving of simultaneous equation using 287.6 nm and 313.2 nm as two wavelengths. Second developed method is based on two wavelength calculation. Two wavelengths selected for estimation of ethamsylate were 274.4 nm and 301.2 nm while that for mefenamic acid were 304.8 nm and 320.4 nm. Both the developed methods obey Beer’s law in the concentration ranges employed for the respective methods. The results of analysis were validated statistically and by recovery studies. Key words: Ethamsylate, mefenamic acid, simultaneous analysis, two wavelength calculation method, simultaneous equation method *For correspondence E-mail: goyalanjugoyal@yahoo.co.in 108. Indian Journal of Pharmaceutical Sciences. January - February 2008.

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