Application of rapid and simple liquid chromatography method for determination of bioequivalence of generic lamotrigine tablets in healthy Iranian volunteers

Document Type : Research(Original) Article



A simple and rapid chromatography method was developed for determination of lamotrigine in human plasma. The method was used to compare the pharmacokinetic (PK) parameters of 50 mg generic and the reference lamotrigine (Lamictal) tablets in healthy Iranian volunteers. High performance liquid chromatography - ultraviolet method was developed and validated to determine lamotrigine concentration in plasma samples. The method was linear over the range of 0.1 to 15 µg/ml. The accuracy and precision were within the acceptable range. Limits of detection and quantification were calculated 0.06 and 0.10 µg/mL, respectively. A randomized, single-dose, two-period, two-sequence crossover study was carried out in healthy subjects receiving either the test or the reference products in each period. Pharmacokinetic parameters were determined by non-compartmental PK model. Bioequivalency between the generic and the reference product was investigated according to the guidance for industry issued by US Food Drug Administration. AUC0-t, AUC0-∞ and Cmax were calculated for the generic product 12.50±2.76 µg.h/mL, 15.04±3.66 µg.h/mL and 0.38±0.08 µg/mL, respectively. The 90% confidence interval for the test/reference ratios were laid in the range of 0.80-1.25 for the log-transformed PK parameters. The generic product is bioequivalent and can be prescribed by practitioners while indicated, however the AUC and Cmax were lower in Iranian population if compared to the literature, which requires further investigations.


  1. Stefan H, Feuerstein TJ. Novel anticonvulsant drugs. Pharmacology & Therapeutics. 2007;113(1):165-83.
  2. Biton V. Pharmacokinetics, toxicology and safety of lamotrigine in epilepsy. Expert Opinion on Drug Metabolism & Toxicology. 2006;2(6):1009-18.
  3. Andre P, Novy J, Decosterd LA, Buclin T, Rothuizen LE. Therapeutic Drug Monitoring of Antiepileptic Drugs in the 21st Century. 2010.
  4. McDowall RD, Doyle E, Murkitt GS, Picot VS. Sample preparation for the HPLC analysis of drugs in biological fluids. Journal of Pharmaceutical and Biomedical Analysis. 1989;7(9):1087-96.
  5. Emami J, Ghassami N, Ahmadi F. Development and validation of a new HPLC method for determination of lamotrigine and related compounds in tablet formulations. Journal of Pharmaceutical and Biomedical Analysis. 2006;40(4):999-1005.
  6. Croci D, Salmaggi A, de Grazia U, Bernardi G. New High-Performance Liquid Chromatographic Method for Plasma/Serum Analysis of Lamotrigine. Therapeutic Drug Monitoring. 2001;23(6):665-8.
  7. Torra M, Rodamilans M, Arroyo S, Corbella J. Optimized Procedure for Lamotrigine Analysis in Serum by High-Performance Liquid Chromatography Without Interferences From Other Frequently Coadministered Anticonvulsants. Therapeutic Drug Monitoring. 2000;22(5):621-5.
  8. Bompadre S, Tagliabracci A, Battino M, Giorgetti R. Determination of lamotrigine in whole blood with on line solid phase extraction. J Chromatogr B Analyt Technol Biomed Life Sci. 2008;863(1):177-80.
  9. Castel-Branco MM, Almeida AM, Falcão AC, Macedo TA, Caramona MM, Lopez FG. Lamotrigine analysis in blood and brain by high-performance liquid chromatography. Journal of Chromatography B: Biomedical Sciences and Applications. 2001;755(1–2):119-27.
  10. Böttiger Y, Svensson J-O, Ståhle L. Lamotrigine Drug Interactions in a TDM Material. Therapeutic Drug Monitoring. 1999;21(2):171-4.
  11. Hart AP, Mazarr-Proo S, Blackwell W, Dasgupta A. A Rapid Cost-Effective High-Performance Liquid Chromatographic (HPLC) Assay of Serum Lamotrigine After Liquid-Liquid Extraction and Using HPLC Conditions Routinely Used for Analysis of Barbiturates. Therapeutic Drug Monitoring. 1997;19(4):431-5.
  12. Sane R, Francis M, Deo A. Bioequivalence study of lamotrigine tablets in healthy male human volunteers. Indian drugs. 1998;35(9):570-3.
  13. Srichaiya A, Longchoopol C, Oo-Puthinan S, Sayasathid J, Sripalakit P, Viyoch J. Bioequivalence of generic lamotrigine 100-mg tablets in healthy Thai male volunteers: A randomized, single-dose, two-period, two-sequence crossover study. Clinical Therapeutics. 2008;30(10):1844-51.