Journal of Chinese Pharmaceutical Sciences ›› 2018, Vol. 27 ›› Issue (12): 832-839.DOI: 10.5246/jcps.2018.12.084

• Original articles • Previous Articles     Next Articles

Development of a simple and rapid method to measure the free fraction of lamotrigine in plasma using HPLC: applications for therapeutic drug monitoring

Huanxin Wang, Yaxin Sun, Shansen Xu, Tong Lu, Yanan Chen, Limei Zhao*   

  1. Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, 110004, Liaoning Province, China
  • Received:2018-07-20 Revised:2018-09-07 Online:2018-12-30 Published:2018-10-16
  • Contact: Tel.: +86-24-96615-71111; Fax: +86-24-23925108, E-mail:
  • Supported by:

    Liaoning Province Natural Science Foundation of China (Grant No. 2013021079).


Lamotrigine (LTG) is a widely used antiepileptic drug (AED) for the treatment of new-onset, as well as refractory epilepsy. Due to the narrow treatment window and large individual variability in the pharmacokinetics and pharmacodynamics of LTG, therapeutic drug monitoring (TDM) is necessary in clinical practice to guide dose adjustments. Individual differences and drug combinations can also affect protein binding rate, which further affects the unbound concentration of LTG. The unbound fraction is more closely related to adverse reactions and therapeutic efficacy than total concentration. Therefore, it may be more meaningful to determine the unbound LTG concentration in plasma than the total concentration.Unbound LTG in plasma was extracted by ultrafiltration. High-performance liquid chromatography (HPLC) was used to measure unbound LTG concentration. This method was validated by studies of its selectivity, linearity, lower limit of quantification (LLOQ), accuracy, precision, recovery, and stability.The method was validated over a linear range of 0.2 to 10.0 μg·mL1, and its LLOQ was 0.2 μg·mL1. The method’s relative standard deviations (RSDs) for intra-day and inter-day precision were less than 15%, and its accuracy (RE) was ±4.69%. The recoveries of unbound LTG at three different concentrations satisfied the requirements for the analysis of biological samples, and no significant degradation of LTG was observed under different storage conditions.A simple HPLC method showed good performance when used to measure unbound LTG concentration. This method might be used to study the relationship between unboundLTG concentrations and its effectiveness according to TDM.

Key words: Lamotrigine, Unbound concentration, Ultrafiltration, HPLC, Therapeutic drug monitoring

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