A highly simple, rapid, sensitive and selective method is developed for spectrophotometric determination of gabapentin in pure form as well as in pharmaceutical formulations. The method is based on the formation of a yellow Schiff base derived from the condensation of gabapentin drug (1-amino methyl) cyclo hexane acetic acid and 2,5-dihydroxybenzaldehyde (DHBA) exhibiting a maximum absorbance at 445 nm. The composition, molar absorptivity and effect of different excipient have been determined spectrophotometrically. Under optimized experimental conditions, Beer’s law is obeyed in the concentration range 2.57 - 37.25 μg/ml. The method is validated with respect to accuracy, precision, limit of detection and limit of quantification. The Sandell sensitivity, correlation coefficient and regression equation are calculated. The equilibrium constant and free energy change using Benesi-Hildebrand plot are also determined. The Schiff base derived from condensation of gabapentin with DHBA is also synthesized and characterized. The condensation reaction mechanism has been proposed.
Gabapentin, 2, 5-Dihydroxybenzaldehyde, Pharmaceutical Formulations, Spectrophotometric Analysis
Saleh, M. , Youssef, A. , Hashem, E. and Abdel-Kader, D. (2014) A Novel Spectrophotometric Method for Determination of Gabapentin in Pharmaceutical Formulations Using 2,5-Dihydroxybenzaldehyde. Computational Chemistry, 2, 22-30. doi: 10.4236/cc.2014.22004.
[1] Goa, K.L. and Sokrin, E.M. (1993) Gabapentin: A Review of Its Pharmacological Properties and Clinical Potential in Epilepsy. Drugs, 46, 409-427. http://dx.doi.org/10.2165/00003495-199346030-00007
[2] Etwes, R.D.C. and Binnie, C.D. (1996) Clinical Pharmacokinetics of the Newer Antiepileptic Drugs: Lamotrigine, Vigabatrin, Gabapentin and Oxcarbazepine. Clinical Pharmacokinetics, 30, 403-415.
http://dx.doi.org/10.2165/00003088-199630060-00001
[3] Hengy, H. and Kolle, E.U. (1985) Determination of Gabapentin in Plasma and Urine by High-Performance Liquid Chromatography and Pre-Column Labelling for Ultraviolet Detection. Journal of Chromatography B: Biomedical Sciences and Applications, 341, 473-478.
http://dx.doi.org/10.1016/S0378-4347(00)84064-5
[4] Juenke, J.M., Brown, P.L., Mc Millin, G.A. and Urry, F.M. (2003) Procedure for the Monitoring of Gabapentin with 2,4,6-Trinitrobenzene Sulphonic Acid Derivatizaiton Followed by HPLC with Ultraviolet Detection. Clinical Chemistry, 49, 1198-1201. http://dx.doi.org/10.1373/49.7.1198
[5] Wad, N. and Kramer, G. (1998) Sensitive High-Perfomance Liquid Chromatographic Method with Fluorometric Deterction for the Simultaneous Determination of Gabapentin and Vigabatrin in Serum and Urine. Journal of Chromatography B: Biomedical Sciences and Applications, 705, 54-158.
http://dx.doi.org/10.1016/S0378-4347(97)00521-5
[6] Zhu, Z. and Neirinck, L. (2002) High-Performance Liquid Chromatographic Method for the Determination of Gabapentin in Human Plasma. Journal of Chromatography B: Biomedical Sciences and Applications, 779, 307-312.
[7] Forrest, G., Sills, G.J., Leach, J.P. and Brodie, M.J. (1996) Determination of Gabapentin in Plasma by High-Performance Liquid Chromatography. Journal of Chromatography B: Biomedical Sciences and Applications, 681, 421-425. http://dx.doi.org/10.1016/0378-4347(96)00074-6
[8] Juergens, U.H., May, T.W. and Rambeck, B. (1996) Simultaneous HPLC Determination of Vigabatrin and Gabapentin in Serum with Automated Pre-injection Derivatizaiton. Journal of Liquid Chromatography and Related Technology, 19, 1459-1471.
http://dx.doi.org/10.1080/10826079608007195
[9] Ratnaraj, N. and Patsalos, P.N. (1998) Simultaneous HPLC Determination of Vigabatrin and Gabapentin in Serum with Automated Pre-Injection Derivatizaiton. Therapeutic Drug Monitoring, 20, 430-434. http://dx.doi.org/10.1097/00007691-199808000-00013
[10] Jiang, Q. and Li, S. (1999) Rapid High-Performance Liquid Chromatographic Determination of Serum Gabapentin. Journal of Chromatography B: Biomedical Sciences and Applications, 727, 119-123.
http://dx.doi.org/10.1016/S0378-4347(99)00027-4
[11] Tang, P.H., Miles, M.V., Glauser, T.A. and Grauw, T.D. (1999) Automated Microanalysis of Gabapentin in Human Serum by High-Performance Liquid Chromatography with Fluorometric Detection. Journal of Chromatography B: Biomedical Sciences and Applications, 727, 125-129.
http://dx.doi.org/10.1016/S0378-4347(99)00077-8
[12] Chollet, D.F., Goumaz, L., Juliano, C. and Anderegg, G. (2000) Fast Isocratic High-Performance liquid Chroamatographic Assay Method for the Simultaneous Determination of Gabapentin and Vigabatrin in Human Serum. Journal of Chromatography B: Biomedical Sciences and Applications, 746, 311-314. http://dx.doi.org/10.1016/S0378-4347(00)00327-3
[13] Gauthier, J.D. and Gupta, R. (2002) Determination of Gabapentin in Plasma by Liquid Chromatography with Fluorescence Detection after Solid-Phase Extraction with C18 Column. Clinical Chemistry, 48, 2259-2261.
[14] Vermeij, T.A.C. and Edelbroek, P.M. (2004) Simultaneous High Performance Liquid Chromatographic Analysis of Pregabalin, Gabapentin and Vigabatrin in Human Serum by Precolumn Derivatization with O-phthaldialdehyde and Fluorescenc Detection. Journal of Chromatography B: Biomedical Sciences and Applications, 810, 297-303.
[15] Belal, F., Abdin, H., Al-Majed, A. and Khalil, N.Y. (2002) Spectrofluorimetric Determination of Vigabatrin and Gabapentin in Urine and Dosage Forms Through Derivatization with Fluorescamine. Journal of Pharmaceutical and Biomedical Analysis, 27, 253-260.
http://dx.doi.org/10.1016/S0731-7085(01)00503-9
[16] Hassan, E.M., Belal, F., Al-Deeb, O.A. and Khalil, N.Y. (2001) Spectrofluorimetric Determination of Vigabatrin and Gabapentin in Dosage Forms and Spiked Plasma Samples through Derivatization with 4-Chloro-7-Nitrobenzo-2-Oxa-1,3-Diazole. Journal of AOAC International, 84, 1017-1024.
[17] Wolf, C.E., Saady, J.J. and Poklis, A. (1996) Determination of Gabapentin in Serum Using Solid-Phase Extraction and Gas-Liquid Chromatography. Journal of Analytical Toxicology, 20, 498-501.
http://dx.doi.org/10.1093/jat/20.6.498
[18] Hooper, W.D., Kavanagh, M.C. and Dickinson, R.G. (1990) Determination of Gabapentin in Plasma and Urine by Capillary Column Gas Chromatography. Journal of Chromatography B: Biomedical Sciences and Applications, 529, 167-174. http://dx.doi.org/10.1016/S0378-4347(00)83818-9
[19] Kushnir, M.M., Crossett, J., Brown, P.I. and Urry, F.M. (1999) Analysis of Gabapentin in Serum and Plasma by Solid-Phase Extraction and Gas-Chromatography-Mass Spectrometry for Therapeutic Drug Monitoring. Journal of Analytical Toxicology, 23, 1-6. http://dx.doi.org/10.1093/jat/23.1.1
[20] Hashem, E.Y. and Youssef, A.K. (2013) Spectrophotometric Determination of Norepinephrine with Sodium Iodate and Determination of Its Acidity Constants. Journal of Applied Spectroscopy, 80, 258-264. http://dx.doi.org/10.1007/s10812-013-9755-y
[21] Abdellatef, H.E. and Khalil, H.M. (2003) Colorimetric Determination of Gabapentin in Pharmaceutical Formulation. Journal of Pharmaceutical and Biomedical Analysis, 31, 209-214.
http://dx.doi.org/10.1016/S0731-7085(02)00572-1
[22] Galande, V.R., Baheti, K.G. and Dehghan, M.H. (2010) UV-VIS Spectrophotometric Method for Estimation of Gabapentin and Methylcobalamin in Bulk and Tablet. International Journal of Chemical Technological Research, 2, 695-699.
[23] Siddiqui, F.A., Arayne, M.S., Sultana, N., Qureshi, F., Mirza, A.Z., Zuberi, M.H., Bahadur, S.S., Afrdi, N.S., Shamshad, H. and Rehman, N. (2010) Spectrophotometric Determination of Gabapentin in Pharmaceutical Formulations Using Ninhydrin and π-Acceptors. European Journal of Medicinal Chemistry, 45, 2761-2767. http://dx.doi.org/10.1016/j.ejmech.2010.02.058
[24] Foster, R. (1969) Organic Charge Transfer Complexes. Academic Press, London.
[25] Melby, L.R. (1970) The Chemistry of the Cyano Group. Intersciences Publisher, John Wiley and Sons, New York.
[26] Rao, C.N.R., Bhat, S.N. and Dwedi, P.C. (1972) Spectroscopy of Electron Donor-Acceptor Systems. Applied Spectroscopic Reviews, 5, 1-170. http://dx.doi.org/10.1080/05704927208081699
[27] Rahman, N. and Azmi, S.N.H. (2001) Spectrophotometric Method for the Determination of Ambdipine Besylate with Ninhydrin in Drug Formaulations. Il Farmaco, 56, 731-735.
http://dx.doi.org/10.1016/S0014-827X(01)01093-X
[28] Nobrega, J.D.A., Fatibello-Filho, O. and Vieira, I.D.C. (1994) Flow Injection Spectrophotometric Determination of Aspartame in Dietary Products. Analyst, 119, 2101-2104.
[29] Molnar-Perl, I. and Pinter-Szakacs, M. (1989) Spectrophotometric Determination of Tryptophan in Intact Proteins by the Acid Ninhydrin Method. Analytical Biochemistry, 177, 16-19.
http://dx.doi.org/10.1016/0003-2697(89)90005-5
[30] Gorog, S. (1995) Ultraviolet-Visible Spectrophotometry in Pharmaceutical Analysis. CRC Press, New York.
[31] Osman, A.H., Saleh, M.S. and Mahmoud, S.M. (2004) Synthesis, Characterization, and Photochemical Studies of Some Copper Complexes of Schiffs Bases Derived from 3-Hydraziono-6-methyl[1,2,4]triazin-5(4H)one. Synthesis and Reactivity in Inorganic and Metal Organic Chemistry, 34, 1069-1085. http://dx.doi.org/10.1081/SIM-120039258
[32] Job, P. (1928) Formation and Stability of Inorganic Complexes in Solution. Ann. Chim., 9, 113-203.
[33] Benesi, H.A. and Hildebrand, J.H. (1949) A Spectrophotometric Investigation of Interaction of Iodine with Aromatic Hydrocarbons. Journal of the American Chemical Society, 71, 2703-2707.
http://dx.doi.org/10.1021/ja01176a030
[34] Martin, A.N. and Swarbrick, J. (1969) Physical Pharmacy. 3rd Edition, Lee & Febiger, New York.
[35] Gujral, R.S., Haque, S.M. and Shanker, P. (2009) A Sensitive UV Spectrophotometric Method for the Determination of Gabapentin. European Journal of Chemistry, 6, 163-170.
[36] Ambalal, P.S. and Natavarlal, P. (2011) Visible Spectrophotometric Methods for Determination of Gabapentin in Pharmaceutical Tablet and Capsule Dosage Forms. Asian Journal of Pharmacy and Life Science, 1, 239-249.