Determination Of Lamotrigine In Plasma Research Articles

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

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. 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 276.0nm for lamotrigine and chloramphenicol, respectively. The method was linear concentration dependence within the range of 0.1-10µg/ml, with a mean coefficient of correlation r = 0.993. The limit of detection (LOD) was 0.04µg/ml and the limit of quantification (LOQ) was 0.1µg/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). 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.

A new grey relational analysis application in analytical chemistry: Natural deep eutectic solvent as a green extractant for HPLC determination of lamotrigine in plasma

Developing new, eco-friendly solvents which would meet technological and economic demands is perhaps the most popular aspects of Green Chemistry. Natural deep eutectic solvents (NADES) fully represent green chemistry principles. In this sense a new green vortex-assisted NADES-based microextraction (VA-NADES-ME) was established, for the first time, for the extraction of lamotrigine from human plasma samples using NADES, as a green extractant alternative to hazard organic solvents. Then extract was determined by high performance liquid chromatography with ultraviolet detection (HPLC–UV). The mixture of (choline chloride/ethylene glycol) as NADES was found to be the best candidate for extracting lamotrigine. Grey relational analysis-based Taguchi method was utilized as a chemometric protocol for multiobjective optimization of different HPLC performance parameters. The optimum mobile phase was a mixture of water with 0.3 % triethylamine in 0.02 M H3PO4 (adjusted to pH 5.5) and acetonitrile (70:30 v/v) with an overall pH 6. Finally, the confirmation test was performed to validate the predicted optimal results and established an improvement of 32.84 % from the initial design. The mobile phase was eluted in an isocratic mode with a flow rate of 0.8 mL/min and UV detection at 310 nm. The retention times of lamotrigine and tinidazole (internal standard) were 4.7 and 3.4 min, respectively. Proposed method was linear over the concentration range of 0.1–15.0 μg mL−1. The greenness profile was assessed using Analytical GREEnness metric approach which assured the greenness of the proposed method compared with other reported methods.

A rapid liquid chromatographic method for the determination of lamotrigine in plasma

A rapid, sensitive and simple high-performance liquid chromatographic (HPLC) method for the determination of lamotrigine in plasma is described. The drug was extracted from 100 μl of plasma with chloroform:isopropanol (95:5% v/v) in the presence of 100 μl of phosphate buffer (10 mM). The extract was evaporated and the residue was reconstituted with mobile phase and injected onto the HPLC system. The drug and the internal standard (chloramphenicol) were eluted from a Symmetry C 18 stainless steel column at ambient temperature with a mobile phase consisting of 0.01 M potassium phosphate–acetonitrile–methanol (70:20:10% v/v/v), adjusted to pH 6.7, at a flow rate of 1.3 ml min −1 and the detector was monitored at 214 nm. Quantitation was achieved by measurement of the peak-area ratio of the drug to the internal standard and the lower limit of detection for lamotrigine in plasma was 20 ng ml −1. The intraday precision ranged from 3.34 to 6.12% coefficient of variation (CV) and the interday precision ranged from 2.15 to 8.34% CV. The absolute and relative recoveries of lamotrigine ranged from 86.93 to 90.71% and from 95.18 to 107.13%, respectively. The method was applied in studying the pharmacokinetics of lamotrigine administered orally to rabbits. This reliable micro-method would have application in pharmacokinetic studies of lamotrigine where only small sample sizes are available, e.g. paediatric patients.