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Validated Spectrofluorimetric Method for the Determination of Lamotrigine in Tablets and Human Plasma Through Derivatization with o-phthalaldehyde

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Abstract

A sensitive, simple and selective spectrofluorimetric method was developed for the determination of Lamotrigine (LMT) in pharmaceutical formulations and biological fluids. The method is based on reaction of LMT with o-phthalaldehyde in presence of 2-mercaptoethanol in borate buffer of pH 9.8 to yield a highly fluorescent derivative that is measured at 448 nm after excitation at 337 nm. The different experimental parameters affecting the development and stability of the reaction product were carefully studied and optimized. The fluorescence-concentration plot was rectilinear over the range of 0.1–1.0 µg ml−1 with lower limit of detection (LOD) 0.02 μg ml−1 and limit of quantification (LOQ) 0.06 μg ml−1 respectively. The proposed method was successfully applied to the the analysis of commercial tablets. Statistical comparison of the results obtained by the proposed and reference method revealed no significant difference in the performance of the two methods regarding the accuracy and precision respectively. The proposed method was further extended to the in-vitro and in-vivo determination of the drug in spiked and real human plasma. The mean percentage recoveries in spiked and real human plasma (n = 3) were 95.78 ± 1.37 and 90.93 ± 2.34 respectively. Interference arising from co-administered drugs was also studied. A proposal for the reaction pathway with o-phthalaldehyde was postulated.

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References

  1. Goa KL, Ross SR, Chrisp P (1993) Lamotrigine: a review of its pharmacological properties and clinical efficacy in epilepsy. Drugs 46:152–176

    Article  CAS  PubMed  Google Scholar 

  2. Messenheimer J, Mullens EL, Giorgi L, Young F (1998) Safety review of adult clinical expeiance with lamotrigine. Drug Saf 18:281–296

    Article  CAS  PubMed  Google Scholar 

  3. Pellock M (1997) Overview of lamotrigine and the new antiepileptic drugs: the challenge. J Child Neurol 12:S48–S52

    Article  PubMed  Google Scholar 

  4. Sabers A, Ohman I, Christensen J, Tomson T (2003) Oral contraceptives reduce lamotrigine plasma levels. Neurology 61:570–571

    CAS  PubMed  Google Scholar 

  5. Youssef NF, Taha EA (2007) Development and validation of spectrophotometric, TLC and HPLC methods for the determination of lamotrigine in presence of its impurity. Chem Pharm Bull 55:541–545

    Article  CAS  PubMed  Google Scholar 

  6. Burgoa Calvo ME, Renedo OD, Arcos Martínez MJ (2007) Determination of lamotrigine by adsorptive stripping voltammetry using silver nanoparticle-modified carbon screen-printed electrodes. Talanta 74:59–64

    Article  CAS  PubMed  Google Scholar 

  7. Burgoa Calvo ME, Renedo OD, Arcos Martínez MJ (2005) Optimization of the experimental parameters in the determination of lamotrigine by adsorptive stripping voltammetry. Anal Chim Acta 549:74–80

    Article  CAS  Google Scholar 

  8. Emami J, Ghassami N, Ahmadi F (2006) Development and validation of a new HPLC method for determination of lamotrigine and related compounds in tablet formulations. J Pharm Biomed Anal 40:999–1005

    Article  CAS  PubMed  Google Scholar 

  9. Saracino MA, Bugamelli F, Conti M, Amore M, Raggi MA (2007) Rapid HPLC analysis of the antiepileptic lamotrigine and its metabolites in human plasma. J Sep Sci 30:2249–2255

    Article  CAS  PubMed  Google Scholar 

  10. Beck O, Ohman I, Nordgren HK (2006) Determination of lamotrigine and its metabolites in human plasma by liquid chromatography-mass spectrometry. Ther Drug Monit 28:603–607

    Article  CAS  PubMed  Google Scholar 

  11. Zufía L, Aldaz A, Ibáñez N, Viteri C (2009) LC method for the therapeutic drug monitoring of lamotrigine: evaluation of the assay performance and validation of its application in the routine area. J Pharm Biomed Anal 49:547–553

    Article  PubMed  Google Scholar 

  12. Greiner C, Haen E (2007) Development of a simple column-switching high- performance liquid chromatography (HPLC) method for rapid and simultaneous routine serum monitoring of lamotrigine, oxcarbazepine and 10-monohydroxycarbazepine (MHD). J Chromatogr B 854:338–344

    Article  CAS  Google Scholar 

  13. Greiner-Sosanko E, Giannoutsos S, Lower DR, Virji MA, Krasowski MD (2007) Drug monitoring: simultaneous analysis of lamotrigine, oxcarbazepine, 10-hydroxycarbazepine, and zonisamide by HPLC-UV and a rapid GC method using a nitrogen-phosphorus detector for levetiracetam. J Chromatogr Sci 45:616–622

    CAS  PubMed  Google Scholar 

  14. Ching-Ling C, Chen-His C, Yoa-Pu Hu O (2005) Determination of lamotrigine in small volumes of plasma by high-performance liquid chromatography. J Chromatogr B 817:199–206

    Article  Google Scholar 

  15. Bompadre S, Tagliabracci A, Battino M, Giorgetti R (2008) Determination of lamotrigine in whole blood with on line solid phase extraction. J Chromatogr B 863:177–180

    Article  CAS  Google Scholar 

  16. Zheng J, Jann MW, Hon YY, Shamsi SA (2004) Development of capillary zone electrophoresis-electrospray ionization-mass spectrometry for the determination of lamotrigine in human plasma. Electrophoresis 25:2033–2043

    Article  CAS  PubMed  Google Scholar 

  17. Pucci V, Bugamelli F, Baccini C, Raggi MA (2005) Analysis of lamotrigine and its metabolites in human plasma and urine by micellar electrokinetic capillary chromatography. Electrophoresis. 26:935–942

    Article  CAS  PubMed  Google Scholar 

  18. Kand'ár R, Záková P, Lotková H, Kucera O, Cervinková Z, Yoshitake M, Sejima N, Yoshida H, Todoroki K, Nohta H, Yamaguchi M (2007) Determination of reduced and oxidized glutathione in biological samples using liquid chromatography with fluorimetric detection. J Pharm Biomed Anal 43:1382–1387

    Article  PubMed  Google Scholar 

  19. Korös A, Hanczkó R, Jámbor A, Qian Y, Perl A, Molnár-Perl I (2007) Analysis of amino acids and biogenic amines in biological tissues as their o-phthalaldehyde/ethanethiol/fluorenylmethyl chloroformate derivatives by high-performance liquid chromatography. A deproteinization study. J Chromatogr A 1149:46–55

    Article  PubMed  Google Scholar 

  20. Yoshitake M, Sejima N, Yoshida H, Todoroki K, Nohta H, Yamaguchi M (2007) Selective determination of tryptophan-containing peptides through precolumn derivatization and liquid chromatography using intramolecular fluorescence resonance energy transfer detection. Anal Sci 8:949–953

    Article  Google Scholar 

  21. El-Gindy A, Ashour A, Abdel-Fattah L, Shabana MM (2001) Spectrophotometric, septrofluorimetric and LC determination of lisinopril. J Pharm Biomed Anal 25:913–922

    Article  CAS  PubMed  Google Scholar 

  22. Tzanavaras PD, Zacharis CK, Rigas P (2008) Novel automated assay for the quality control of mexiletine hydrochloride formulations using sequential injection and on-line dilution. J Pharm Biomed Anal 48:1254–1260

    Article  CAS  PubMed  Google Scholar 

  23. Munson JW (1981) Pharmaceutical analysis Part A., NY, p 284

  24. Sun Y, Nakashima MN, Takahashi M, Kuroda N, Nakashima K (2002) Determination of bisphenol A in rat brain by microdialysis and column switching high- performance liquid chromatography with fluorescence detection. Biomed Chromatogr 16:319–326

    Article  CAS  PubMed  Google Scholar 

  25. Moffat AC, Osselton MD, Widdop B, Galichet LY (2006) Clark’s analysis of drugs and poisons in pharmaceuticals, body fluids and postmortem material, 4th edn. Pharmaceutical, London Electronic version

    Google Scholar 

  26. International Conference on Harmonization Notes on “Validation of analytical procedures: text and methadology”, Q2(R1) Approval on November 2005 http://www.ich.org/LOB/media/MEDIA417.pdf

  27. Miller JC, Miller JN (2005) Statistics and chemometrics for analytical chemistry, 5th edn. Prentice Hall, England, p 256

    Google Scholar 

  28. Rose J (1964) Advanced physico-chemical experiments. Pitman, London

    Google Scholar 

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Authors and Affiliations

  1. Department of Analytical Chemistry, Mansoura University, Mansoura, 35516, Egypt

    Nahed M. El-Enany, Amina A. Abdelal & Fathalla F. Belal

  2. Department of Medicinal Chemistry, Mansoura University, Mansoura, 35516, Egypt

    Dina T. El-Sherbiny

Authors
  1. Nahed M. El-Enany
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  2. Dina T. El-Sherbiny
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  3. Amina A. Abdelal
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  4. Fathalla F. Belal
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Correspondence to Nahed M. El-Enany.

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El-Enany, N.M., El-Sherbiny, D.T., Abdelal, A.A. et al. Validated Spectrofluorimetric Method for the Determination of Lamotrigine in Tablets and Human Plasma Through Derivatization with o-phthalaldehyde. J Fluoresc 20, 463–472 (2010). https://doi.org/10.1007/s10895-009-0568-6

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  • DOI: https://doi.org/10.1007/s10895-009-0568-6

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