Analysis of Tolfenamic Acid using a Simple, Rapid, and Stability-indicating Validated HPLC Method


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Abstract

Background:Tolfenamic acid (TA) belongs to the fenamates class of non-steroidal anti-inflammatory drugs. Insufficient information is available regarding the availability of a reliable and validated stability-indicating method for the assay of TA.

Objective:A relatively simple, rapid, accurate, precise, economical, robust, and stability-indicating RP-HPLC method has been developed to determine TA in pure and tablet dosage forms.

Methods:The method was validated according to the ICH guideline, and parameters like linearity, range, selectivity, accuracy, precision, robustness, specificity, and solution stability were determined. TLC and FTIR spectrometry were used to ascertain the purity of TA. The specificity was determined with known impurities and after performing forced degradation, while the robustness was established by Plackett-Burman's experimental design. The mobile phase used for the analysis was acetonitrile and water (90:10, v/v) at pH 2.5. The detection of the active drug was made at 280 nm using a C18 column (tR = 4.3 min.). The method's ap-plicability was also checked for the yellow polymorphic form of TA.

Results:The results indicated that the method is highly accurate (99.39-100.80%), precise (<1.5% RSD), robust (<2% RSD), and statistically comparable to the British Pharmacopoeia method with better sensitivity and specificity.

Conclusion:It was observed that the stress degradation studies do not affect the method's accuracy and specificity. Hence the proposed method can be used to assay TA and its tablet dosage form.

About the authors

Sadia Kazi

Baqai Institute of Pharmaceutical Sciences, Baqai Medical University

Email: info@benthamscience.net

Muhammad Sheraz

Baqai Institute of Pharmaceutical Sciences,, Baqai Medical University

Email: info@benthamscience.net

Syed Musharraf

H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences,, University of Karachi

Email: info@benthamscience.net

Sofia Ahmed

Baqai Institute of Pharmaceutical Sciences,, Baqai Medical University

Email: info@benthamscience.net

Raheela Bano

Dow College of Pharmacy, Dow University of Health Sciences

Email: info@benthamscience.net

Faraz Haq

H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi

Email: info@benthamscience.net

Zubair Anwar

Baqai Institute of Pharmaceutical Sciences,, Baqai Medical University

Author for correspondence.
Email: info@benthamscience.net

Raahim Ali

, Baqai Institute of Pharmaceutical Sciences

Email: info@benthamscience.net

References

  1. Rozou, S.; Michaleas, S.; Antoniadou-Vyza, E. Supramolecular interactions between tolfenamic acid and various cyclodextrins: Effects of complexation on physicochemical and spectroscopic data. Pharm. Pharmacol. Commun., 1999, 5(2), 79-84. doi: 10.1211/146080899128734497
  2. Kovala-Demertzi, D.; Hadjipavlou-Litina, D.; Primikiri, A.; Staninska, M.; Kotoglou, C.; Demertzis, M.A. Anti-inflammatory, antiproliferative, and radical-scavenging activities of tolfenamic acid and its metal complexes. Chem. Biodivers., 2009, 6(6), 948-960. doi: 10.1002/cbdv.200800120 PMID: 19551737
  3. British Pharmacopoeia. In: Monograph on tolfenamic acid; Her Majesty’s Stationary Office: London, UK, 2023.
  4. Sweetman, S. Martindale The Complete Drug Reference; Pharmaceutical Press: London, UK, 2013, pp. 1689-1699.
  5. Pan, L.; Gardner, C.L.; Pagliai, F.A.; Gonzalez, C.F.; Lorca, G.L. Identification of the tolfenamic acid binding pocket in PrbP from Liberibacter asiaticus. Front. Microbiol., 2017, 8, 1591. doi: 10.3389/fmicb.2017.01591 PMID: 28878750
  6. British National Formulary (BNF) 84; BMJ Group and Royal Pharmaceutical Society, Pharmaceutical Press: London, UK, 2022, pp. 530-531.
  7. Basha, R.; Ingersoll, S.B.; Sankpal, U.T.; Ahmad, S.; Baker, C.H.; Edwards, J.R.; Holloway, R.W.; Kaja, S.; Abdelrahim, M. Tolfenamic acid inhibits ovarian cancer cell growth and decreases the expression of c-Met and survivin through suppressing specificity protein transcription factors. Gynecol. Oncol., 2011, 122(1), 163-170. doi: 10.1016/j.ygyno.2011.03.014 PMID: 21496890
  8. Liggett, J.L.; Zhang, X.; Eling, T.E.; Baek, S.J. Anti-tumor activity of non-steroidal anti-inflammatory drugs: Cyclooxygenase-independent targets. Cancer Lett., 2014, 346(2), 217-224. doi: 10.1016/j.canlet.2014.01.021 PMID: 24486220
  9. Feldman, D.; Leahy, E.; Lee, S.H. Chemopreventive properties of tolfenamic acid: A mechanistic review. Curr. Med. Chem., 2018, 25(14), 1598-1608. doi: 10.2174/0929867324666170414155107 PMID: 28413959
  10. Adwan, L.I.; Basha, R.; Abdelrahim, M.; Subaiea, G.M.; Zawia, N.H. Tolfenamic acid interrupts the de novo synthesis of the β-amyloid precursor protein and lowers amyloid beta via a transcriptional pathway. Curr. Alzheimer Res., 2011, 8(4), 385-392. doi: 10.2174/156720511795745285 PMID: 21557719
  11. Subaiea, G.M.; Alansi, B.H.; Serra, D.A.; Alwan, M.; Zawia, N.H. The ability of tolfenamic acid to penetrate the brain: A model for testing the brain disposition of candidate Alzheimer’s drugs using multiple platforms. Curr. Alzheimer Res., 2011, 8(8), 860-867. doi: 10.2174/156720511798192691 PMID: 21605061
  12. Adwan, L.; Subaiea, G.M.; Zawia, N.H. Tolfenamic acid downregulates BACE1 and protects against lead-induced upregulation of Alzheimer’s disease related biomarkers. Neuropharmacology, 2014, 79, 596-602. doi: 10.1016/j.neuropharm.2014.01.009 PMID: 24462621
  13. Moffat, A.C.; Osselton, M.D.; Widdop, B. Clarke’s Analysis of Drugs and Poisons, 4th; Pharmaceutical Press: London, UK, 2011, pp. 1646-1647.
  14. Ahmed, S.; Mustaan, N.; Sheraz, M.A.; Nabi, S.A.A.; Ahmad, I. Validation of a UV spectrometric method for the assay of tolfenamic acid in organic solvents. J. Pharm., 2015, 2015, 1-8. doi: 10.1155/2015/216249 PMID: 26783497
  15. Ahmed, S.; Sheraz, M.A.; Ahmad, I. Tolfenamic Acid.Profiles of Drug Substances, Excipients, and Related Methodology; Brittain, H.G., Ed.; Academic Press: Elsevier: Cambridge, USA, 2018, Vol. 43, pp. 255-319.
  16. Abdelwahab, N.S.; Ali, N.W.; Zaki, M.M.; Abdelkawy, M. Validated chromatographic methods for simultaneous determination of tolfenamic acid and its major impurities. J. Chromatogr. Sci., 2015, 53(4), 484-491. doi: 10.1093/chromsci/bmu071 PMID: 25016532
  17. Rozou, S.; Antoniadou-Vyza, E. An improved HPLC method overcoming Beer’s law deviations arising from supramolecular interactions in tolfenamic acid and cyclodextrins complexes. J. Pharm. Biomed. Anal., 1998, 18(4-5), 899-905. doi: 10.1016/S0731-7085(98)00227-1 PMID: 9919995
  18. Van Eerdenbrugh, B.; Baird, J.A.; Taylor, L.S. Crystallization tendency of active pharmaceutical ingredients following rapid solvent evaporation--classification and comparison with crystallization tendency from undercooled melts. J. Pharm. Sci., 2010, 99(9), 3826-3838. doi: 10.1002/jps.22214 PMID: 20533435
  19. Gallo, P.; Fabbrocino, S.; Dowling, G.; Salini, M.; Fiori, M.; Perretta, G.; Serpe, L. Confirmatory analysis of non-steroidal anti-inflammatory drugs in bovine milk by high-performance liquid chromatography with fluorescence detection. J. Chromatogr. A, 2010, 1217(17), 2832-2839. doi: 10.1016/j.chroma.2010.02.047 PMID: 20227702
  20. Gallo, P.; Fabbrocino, S.; Vinci, F.; Fiori, M.; Danese, V.; Nasi, A.; Serpe, L. Multi-residue determination of non-steroidal anti-inflammatory drug residues in animal serum and plasma by HPLC and photo-diode array detection. J. Chromatogr. Sci., 2006, 44(10), 585-590. doi: 10.1093/chromsci/44.10.585 PMID: 17254366
  21. de Melo da Silva, L.; Pereira Cavalcante, R.; Fabbro Cunha, R.; Gozzi, F.; Falcao Dantas, R.; de Oliveira, S.C.; Machulek, A. Tolfenamic acid degradation by direct photolysis and the UV-ABC/H2O2 process: Factorial design, kinetics, identification of intermediates, and toxicity evaluation. Sci. Total Environ., 2016, 573, 518-531. doi: 10.1016/j.scitotenv.2016.08.139 PMID: 27575359
  22. Nielsen-Kudsk, F. HPLC-determination of some antiinflammatory, weak analgesic and uricosuric drugs in human blood plasma and its application to pharmacokinetics. Acta Pharmacol. Toxicol., 1980, 47(4), 267-273. doi: 10.1111/j.1600-0773.1980.tb03653.x PMID: 6970498
  23. Pentikäinen, P.J.; Neuvonen, P.J.; Backman, C. Human pharmacokinetics of tolfenamic acid, a new anti-inflammatory agent. Eur. J. Clin. Pharmacol., 1981, 19(5), 359-365. doi: 10.1007/BF00544587 PMID: 7238564
  24. Niopas, I.; Georgarakis, M. Pharmacokinetics of tolfenamic acid in pediatric patients after single oral dose. Eur. J. Drug. Meta. Pharmacol., 1995, 20, 293-296.
  25. McKellar, Q.A.; Lees, P.; Gettinby, G. Pharmacodynamics of tolfenamic acid in dogs. Evaluation of dose response relationships. Eur. J. Pharmacol., 1994, 253(3), 191-200. doi: 10.1016/0014-2999(94)90191-0 PMID: 8200415
  26. Landoni, M.F.; Cunningham, F.M.; Lees, P. Pharmacokinetics and pharmacodynamics of tolfenamic acid in calves. Res. Vet. Sci., 1996, 61(1), 26-32. doi: 10.1016/S0034-5288(96)90106-X PMID: 8819190
  27. Lefebvre, H.P.; Laroute, V.; Alvinerie, M.; Schneider, M.; Vinclair, P.; Braun, J.P.; Toutain, P.L. The effect of experimental renal failure on tolfenamic acid disposition in the dog. Biopharm. Drug Dispos., 1997, 18(1), 79-91. doi: 10.1002/(SICI)1099-081X(199701)18:13.0.CO;2-F PMID: 9008271
  28. Kang, Y.P.; Yu, J.; Huh, Y.; Oh, J.H.; Kwon, C.H.; Lee, S.J.; Ee, J.W.; Kim, G.T.; Lee, J.G.; Lee, J.; Park, J.H.; Kim, Y.S.; Kwon, S.W. Development of high performance liquid chromatography-ultraviolet detection method for screening mebendazole, clorsulon, diaveridine, and tolfenamic acid in animal-based food samples. Drug Test. Anal., 2014, 6(3), 246-256. doi: 10.1002/dta.1467 PMID: 23576386
  29. Mikami, E.; Goto, T.; Ohno, T.; Matsumoto, H.; Inagaki, K.; Ishihara, H.; Nishida, M. Simultaneous analysis of anthranilic acid derivatives in pharmaceuticals and human urine by high-performance liquid chromatography with isocratic elution. J. Chromatogr., Biomed. Appl., 2000, 744(1), 81-89. doi: 10.1016/S0378-4347(00)00233-4 PMID: 10985569
  30. Rozou, S.; Michaleas, S.; Antoniadou-Vyza, E. Study of structural features and thermodynamic parameters, determining the chromatographic behaviour of drug-cyclodextrin complexes. J. Chromatogr. A, 2005, 1087(1-2), 86-94. doi: 10.1016/j.chroma.2005.02.039 PMID: 16130701
  31. Ra, J.S.; Oh, S.Y.; Lee, B.C.; Kim, S.D. The effect of suspended particles coated by humic acid on the toxicity of pharmaceuticals, estrogens, and phenolic compounds. Environ. Int., 2008, 34(2), 184-192. doi: 10.1016/j.envint.2007.08.001 PMID: 17765969
  32. Guan, J.; Zhang, C.; Wang, Y.; Guo, Y.; Huang, P.; Zhao, L. Simultaneous determination of 12 pharmaceuticals in water samples by ultrasound-assisted dispersive liquid-liquid microextraction coupled with ultra-high performance liquid chromatography with tandem mass spectrometry. Anal. Bioanal. Chem., 2016, 408(28), 8099-8109. doi: 10.1007/s00216-016-9913-1 PMID: 27614980
  33. Ma, L.; Li, J.; Xu, L. Aqueous chlorination of fenamic acids: Kinetic study, transformation products identification and toxicity prediction. Chemosphere, 2017, 175, 114-122. doi: 10.1016/j.chemosphere.2017.02.045 PMID: 28211324
  34. Mahghoub, S. Validated RP-HPLC method for quantitative determination of tolfenamic acid and benzyl alcohol in veterinary pharmaceutical preparation. Aus. Chromatogr., 2017, 4, 1046.
  35. Turk, E.; Tekeli, I.O.; Durna Corum, D.; Corum, O.; Altinok Yipel, F.; Ilhan, A.; Emiroglu, S.B.; Uguz, H.; Uney, K. Pharmacokinetics of tolfenamic acid in goats after different administration routes. J. Vet. Pharmacol. Ther., 2021, 44(3), 367-373. doi: 10.1111/jvp.12949 PMID: 33560540
  36. Turk, E.; Tekeli, I.O.; Corum, O.; Durna Corum, D.; Kirgiz, F.C.; Cetin, G.; Arslan Atessahin, D.; Uney, K. Pharmacokinetics of meloxicam, carprofen, and tolfenamic acid after intramuscular and oral administration in Japanese quails (Coturnix coturnix japonica). J. Vet. Pharmacol. Ther., 2021, 44(3), 388-396. doi: 10.1111/jvp.12972 PMID: 33846990
  37. Tay, K.S.; Mansor, N.A. The fate of tolfenamic acid in conventional chlorination and UV/chlorination process. Chem. Zvesti, 2022, 76(11), 6869-6877. doi: 10.1007/s11696-022-02378-8
  38. Blanco-Paniagua, E.; García-Lino, A.M.; García-Mateos, D.; Álvarez, A.I.; Merino, G. Role of the Abcg2 transporter in plasma levels and tissue accumulation of the anti-inflammatory tolfenamic acid in mice. Chem. Biol. Interact., 2021, 345109537 doi: 10.1016/j.cbi.2021.109537 PMID: 34062171
  39. Gao, L.; Zheng, W.Y.; Yang, W.L.; Zhang, X.R. Drug-drug salt forms of vortioxetine with mefenamic acid and tolfenamic acid. J. Mol. Struct., 2022, 1268, 133725. doi: 10.1016/j.molstruc.2022.133725
  40. Guideline, H.T. Harmonised Tripartite Guideline. Validation of Analytical Procedures, Text and Methodology Q2(R1 International Conference on Harmonization of Technical Requirements for Registration of Pharmaceuticals for Human Use,; Geneva, Switzerland, 2005.
  41. Rasmussen, H.T.; Li, W.; Redlich, D.; Jimidar, M.L. HPLC method development.Handbook of Pharmaceutical Analysis by HPLC; Ahuja, S; Dong, M.W., Ed.; Elsevier Inc.: Amsterdam, The Netherlands, 2005. doi: 10.1016/S0149-6395(05)80050-9
  42. Andersen, K.V.; Larsen, S.; Alhede, B.; Gelting, N.; Buchardt, O. Characterization of two polymorphic forms of tolfenamic acid, N-(2-methyl-3-chlorophenyl)anthranilic acid: Their crystal structures and relative stabilities. J. Chem. Soc., Perkin Trans. 2, 1989, 2(10), 1443-1447. doi: 10.1039/p29890001443
  43. Mattei, A.; Li, T. Polymorph formation and nucleation mechanism of tolfenamic acid in solution: An investigation of pre-nucleation solute association. Pharm. Res., 2012, 29(2), 460-470. doi: 10.1007/s11095-011-0574-7 PMID: 21879384
  44. Sheraz, M.A.; Ahmed, S.; Rehman, I. Effect of pH, polymer concentration and molecular weight on the physical state properties of tolfenamic acid. Pharm. Dev. Technol., 2015, 20(3), 352-360. doi: 10.3109/10837450.2013.871027 PMID: 24417663
  45. Surov, A.O.; Szterner, P.; Zielenkiewicz, W.; Perlovich, G.L. Thermodynamic and structural study of tolfenamic acid polymorphs. J. Pharm. Biomed. Anal., 2009, 50(5), 831-840. doi: 10.1016/j.jpba.2009.06.045 PMID: 19632801
  46. Surov, A.O.; Terekhova, I.V.; Bauer-Brandl, A.; Perlovich, G.L. Thermodynamic and structural aspects of some fenamate molecular crystals. Cryst. Growth Des., 2009, 9(7), 3265-3272. doi: 10.1021/cg900002q
  47. Hartmann, C.; Smeyers-Verbeke, J.; Penninckx, W.; Vander Heyden, Y.; Vankeerberghen, P.; Massart, D.L. Reappraisal of hypothesis testing for method validation: Detection of systematic error by comparing the means of two methods or of two laboratories. Anal. Chem., 1995, 67(24), 4491-4499. doi: 10.1021/ac00120a011
  48. Rahman, N.; Khan, S. Circular dichroism spectroscopy: An efficient approach for the quantitation of ampicillin in presence of cloxacillin. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2016, 160, 26-33. doi: 10.1016/j.saa.2016.02.009 PMID: 26909703
  49. Rahman, N.; Sameen, S.; Kashif, M. Spectroscopic study on the interaction of haloperidol and 2, 4-dinitrophenylhydrazine and its application for the quantification in drug formulations. Anal. Chem. Lett., 2016, 6(6), 874-885. doi: 10.1080/22297928.2016.1265898
  50. Usmani, M.; Ahmed, S.; Ali Sheraz, M.; Ahmad, I. Development and validation of a pre-column derivatization HPLC method for the assay of amikacin sulfate in pure and parenteral dosage forms. Curr. Pharm. Anal., 2019, 15(5), 511-520. doi: 10.2174/1573412914666180314121213
  51. Gilpin, R.K.; Zhou, W. Infrared studies of the polymorphic states of the fenamates. J. Pharm. Biomed. Anal., 2005, 37(3), 509-515. doi: 10.1016/j.jpba.2004.11.009 PMID: 15740911
  52. Jabeen, S.; Dines, T.J.; Leharne, S.A.; Chowdhry, B.Z. Raman and IR spectroscopic studies of fenamates - Conformational differences in polymorphs of flufenamic acid, mefenamic acid and tolfenamic acid. Spectrochim. Acta A Mol. Biomol. Spectrosc., 2012, 96, 972-985. doi: 10.1016/j.saa.2012.07.129 PMID: 22954807
  53. Ahmed, S.; Sheraz, M.A.; Rehman, I.U. Studies on tolfenamic acid-chitosan intermolecular interactions: Effect of pH, polymer concentration and molecular weight. AAPS PharmSciTech, 2013, 14(2), 870-879. doi: 10.1208/s12249-013-9974-9 PMID: 23620261
  54. Ahmed, S.; Sheraz, M.A.; Yorucu, C.; Rehman, I.U. Quantitative determination of tolfenamic acid and its pharmaceutical formulation using FTIR and UV spectrometry. Cent. Eur. J. Chem., 2013, 11, 1533-1541.
  55. Andleeb, S.; Ahmed, S.; Sheraz, M.A.; Anwar, Z.; Ahmad, I. Development and validation of a spectrofluorimetric method for the analysis of tolfenamic acid in pure and tablet dosage form. Luminescence, 2020, 35(7), 1017-1027. doi: 10.1002/bio.3810 PMID: 32419348
  56. Swartz, M.E.; Krull, I.S. Handbook of Analytical Validation, Boca Raton; CRC Press: USA, 2012, pp. 61-100. doi: 10.1201/b12039
  57. Shrivastava, A.; Saxena, P. Validation of Analytical Methods; Methodology and Statistics, CBS Publishers and Distributors: New Dehli, India, 2014.
  58. Ahmed, S.; Khan, A.; Sheraz, M.A.; Bano, R.; Ahmad, I. Development and validation of a stability-indicating HPLC method for the assay of carvedilol in pure and tablet dosage forms. Curr. Pharm. Anal., 2018, 14(2), 139-152. doi: 10.2174/1573412913666170525122146
  59. Singh, R. HPLC method development and validation-an overview. J. Pharm. Edu. Res., 2013, 4, 26-33.
  60. Lister, A.S. Validation of HPLC methods in pharmaceutical analysis. Handbook of Pharmaceutical Analysis by HPLC; Ahuja, S; Dong, M.W., Ed.; Elsevier Inc.: Amsterdam, The Netherlands, 2005, pp. 191-217. doi: 10.1016/S0149-6395(05)80051-0
  61. Thybo, P.; Kristensen, J.; Hovgaard, L. Characterization and physical stability of tolfenamic acid-PVP K30 solid dispersions. Pharm. Dev. Technol., 2007, 12(1), 43-53. doi: 10.1080/10837450601166577 PMID: 17484143
  62. Mattei, A.; Li, T. Interplay between molecular conformation and intermolecular interactions in conformational polymorphism: A molecular perspective from electronic calculations of tolfenamic acid. Int. J. Pharm., 2011, 418(2), 179-186. doi: 10.1016/j.ijpharm.2011.04.062 PMID: 21570454

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