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. 2025 Mar;21(1):1-10.
doi: 10.1007/s12024-024-00812-9. Epub 2024 Apr 10.

Determination of lamotrigine in human plasma by HPLC-PDA. Application to forensic samples

Inés Sánchez-Sellero  1 , Iván Álvarez-Freire  2 , Pamela Cabarcos-Fernández  2 , Lidia Janza-Candal  2 , María Jesús Tabernero-Duque  2 , Ana María Bermejo-Barrera  2
Affiliations

Determination of lamotrigine in human plasma by HPLC-PDA. Application to forensic samples

Inés Sánchez-Sellero et al. Forensic Sci Med Pathol. 2025 Mar.

Abstract

Purpose: Therapeutic drug monitoring of plasma lamotrigine (LTG) has customarily been carried out in order to prevent some its adverse effects. For forensic purposes, determination of LTG in plasma is an useful tool in cases of accidental overdose or suicidal attempts. Currently, there are several analytical methods available including some based on LC tandem mass spectrometry techniques, but simple and accessible LC-UV methods still can be useful for the purpose. Here we report on a new high-performance liquid chromatography method for the determination of lamotrigine in human plasma which has been developed and validated including selectivity, sensitivity, accuracy, precision and recovery studies.

Methods: Lamotrigine and the internal standard chloramphenicol were extracted from plasma using liquid-liquid extraction using small volumes of buffer and ethylacetate. Detection was monitored at 305.7 and 276.0 nm for lamotrigine and chloramphenicol, respectively.

Results: The method was linear concentration dependence within the range of 0.1-10 µg/ml, with a mean coefficient of correlation r = 0.993. The limit of detection (LOD) was 0.04 µg/ml and the limit of quantification (LOQ) was 0.1 µg/ml. Intra and interday precision values were lower than 9.0% at all concentrations studied. The intra and interday accuracy values ranged from - 7.6 to 10.1%. Recovery was found to be 98.9% or higher. The method here described was successfully applied to 11 postmortem blood samples received at the Forensic Sciences Institute of Santiago de Compostela (Spain).

Conclusion: A new HPLC method for the determination of lamotrigine in human plasma was developed and validated. A liquid-liquid extraction using small volumes of buffer and ethylacetate was optimized. The proposed method is suitable for forensic toxicological analysis.

Keywords: Forensic; HPLC–PDA; Lamotrigine; Plasma.

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Conflict of interest statement

Declarations. Conflicts of interest: There are no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Chromatogram of a standard solution of lamotrigine (LTG) and chloramphenicol (IS). Retention times of 5.7 and 8.5 min for LTG and IS, respectively
Fig. 2
Fig. 2
Absorbance spectrum of a standard solution of lamotrigine
Fig. 3
Fig. 3
Absorbance spectrum of a standard solution of chloramphenicol
Fig. 4
Fig. 4
HPLC-PDA chromatogram of a blank human plasma sample spiked with the internal standard (chloramphenicol)
Fig. 5
Fig. 5
Calibration curve for LTG in human plasma
Fig. 6
Fig. 6
HPLC-PDA chromatogram of a postmortem sample received at the Forensic Toxicology Service of the Forensic Sciences Institute of Santiago de Compostela (Spain) and analyzed by the developed and validated method
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References

    1. Nevitt SJ, Sudell M, Cividini S, Marson AG, Tudur Smith C. Antiepileptic drug monotherapy for epilepsy: a network meta-analysis of individual participant data. Cochrane Database Syst Rev. 2022;4(4):CD011412. 10.1002/14651858.CD011412.pub4. - PMC - PubMed
    1. Giri VP, Giri OP, Khan FA, Kumar N, Kumar A, Haque A. Valproic acid versus Lamotrigine as First-line Monotherapy in newly diagnosed idiopathic generalized Tonic-Clonic seizures in adults - a Randomized Controlled Trial. J Clin Diagn Res. 2016;10(7):FC01–4. 10.7860/JCDR/2016/16911.8121. - PMC - PubMed
    1. Betchel NT, Fariba KA, Saadabadi A. Lamotrigine. In: StatPearls, Treasure Island (FL): StatPearls Publishing;2023. https://www.ncbi.nlm.nih.gov/books/NBK470442/. - PubMed
    1. Smith MD, Metcalf CS, Wilcox KS. Pharmacotherapy of the epilepsies. In: Brunton LL, Hilal-Dandan R, Knollmann BC, editors. Goodman & Gilman’s: the pharmacological basis of therapeutics. 13th ed. New York: McGraw Hill; 2018. pp. 303–26.
    1. Yang H, Zhang D, Mei S, Zhao Z. Simultaneous determination of plasma lamotrigine, lamotrigine N2-glucuronide and lamotrigine N2-oxide by UHPLC-MS/MS in epileptic patients. J Pharm Biomed Anal. 2022;220:115017. 10.1016/j.jpba.2022.115017. - PubMed

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