Lamotrigine analysis in blood and brain by high-performance liquid chromatography

Aim: To establish a population pharmacokinetics (PPK) model for lamotrigine (LTG) in Chinese children with epilepsy in order to formulate an individualized dosage guideline. Methods: LTG steady-state plasma concentration data from therapeutic drug monitoring (TDM) were collected retrospectively from 284 patients, with a total of 404 plasma drug concentrations. LTG concentrations were determined using a HPLC method. The patients were divided into 2 groups: PPK model group (n=116) and PPK valid group (n=168). A PPK model of LTG was established with NON-MEM based on the data from PPK model group according to a one-compartment model with first order absorption and elimination. To validate the basic and final model, the plasma drug concentrations of the patients in PPK model group and PPK valid group were predicted by the two models. Results: The final regression model for LTG was as follows: CL (L/h)=1.01*(TBW/27.87) 0.635 *e -0.753*VPA *e 0.868*CBZ *e 0.633*PB , Vd (L)= 16.7*(TBW/27.87). The final PPK model was demonstrated to be stable and effective in the prediction of serum LTG concentrations by an internal and external approach validation. Conclusion: A PPK model of LTG in Chinese children with epilepsy was successfully established with NONMEM. LTG concentrations can be predicted accurately by this model. The model may be very useful for establishing initial LTG dosage guidelines.

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“…This unexplained variability was of similar magnitude to those reported in earlier studies [7,[13][14][15][16][32][33][34] .…”

Section: Discussionsupporting

confidence: 88%

Population pharmacokinetics of lamotrigine in Chinese children with epilepsy

Wang

Qin

et al. 2012

Acta Pharmacol Sin

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“…42,43 Briefly, an aliquot of 100 μL of plasma, previously treated with 10 μL of IS working solution (100 μg/mL), was mixed with 250 μL of 2 mol/L NaOH and then 750 μL of ethyl acetate. The mixtures were vortexed for 2 minutes followed by centrifugation (3,000 g at 15°C for 10 minutes).…”

Section: Processing Of Blood and Brain Tissue For Hplc Analysismentioning

confidence: 99%

“…HPLC analysis of plasma and brain tissue samples was performed using an RP-HPLC system (Agilent 1260 Infinity series, Agilent Technologies, Santa Clara, CA, USA) by previously-described methods, 43,44 with some modifications. A C18 reversed-phase analytical column (250 mm ×4.6 mm, ID 5 μm; Agilent, USA) with a C18 guard column (SecurityGuard C18, 4 mm ×3 mm inner diameter (ID); Phenomenex, Torrance, CA, USA) was used for the separation.…”

mentioning

confidence: 99%

Enhanced brain delivery of lamotrigine with Pluronic® P123-based nanocarrier

Liu¹,

Wang²,

Zhou³

et al. 2014

IJN

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Background P-glycoprotein (P-gp) mediated drug efflux across the blood–brain barrier (BBB) is an important mechanism underlying poor brain penetration of certain antiepileptic drugs (AEDs). Nanomaterials, as drug carriers, can overcome P-gp activity and improve the targeted delivery of AEDs. However, their applications in the delivery of AEDs have not been adequately investigated. The objective of this study was to develop a nano-scale delivery system to improve the solubility and brain penetration of the antiepileptic drug lamotrigine (LTG). Methods LTG-loaded Pluronic ® P123 (P123) polymeric micelles (P123/LTG) were prepared by thin-film hydration, and brain penetration capability of the nanocarrier was evaluated. Results The mean encapsulating efficiency for the optimized formulation was 98.07%; drug-loading was 5.63%, and particle size was 18.73 nm. The solubility of LTG in P123/LTG can increase to 2.17 mg/mL, making it available as a solution. The in vitro release of LTG from P123LTG presented a sustained-release property. Compared with free LTG, the LTG-incorporated micelles accumulated more in the brain at 0.5, 1, and 4 hours after intravenous administration in rats. Pretreatment with systemic verapamil increased the rapid brain penetration of free LTG but not P123/LTG. Incorporating another P-gp substrate (Rhodamine 123) into P123 micelles also showed higher efficiency in penetrating the BBB in vitro and in vivo. Conclusion These results indicated that P123 micelles have the potential to overcome the activity of P-gp expressed on the BBB and therefore show potential for the targeted delivery of AEDs. Future studies are necessary to further evaluate the appropriateness of the nanocarrier to enhance the efficacy of AEDs.

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“…[6][7][8][9][10][11][12] Few methods have been published for its determination including thin layer chromatography which needs 2 h for tank saturation and can not determine lamotrigine in presence of its impurity, 5) gas chromatography, 13) capillary electrophoresis 14,15) and immunoassay. 16,17) In the present study we suggest a simple selective and validated spectrophotometric method using p-chloranilic acid which is used as chromogenic agent for different drugs, it gives an immediate purple chromogen at room temperature.…”

Section: 2)mentioning

confidence: 99%

Development and Validation of Spectrophotometric, TLC and HPLC Methods for the Determination of Lamotrigine in Presence of Its Impurity

Youssef

Taha

2007

Chem. Pharm. Bull.

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Lamotrigine [6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine], is a broad-spectrum antiepileptic, used as monotherapy and as an adjunct with other antiepileptics for treatment of partial and generalized tonic-clonic seizures. Its use to treat neurological lesions and as a tranquilizer also has been studied. 1,2)Lamotrigine is not official in any pharmacopoeia, two stability indicating HPLC methods with UV detection at 210 nm have been reported with either longer analysis time 3) or at definite temperature 40°C.4) The present HPLC method differs from those reported previously 3,4) in terms of mobile phase, pH and temperature, so the main advantage is that the analysis was proceeded at ambient temperature (25Ϯ5°C) not at definite temperature 40°C. Moreover, an UV spectrophotometric method using 0.1 M sodium hydroxide was reported for its determination in tablets.5) But no work seems to have been done on colorimetric assay.Most methods for lamotrigine analysis utilized HPLC technique in biological fluids. [6][7][8][9][10][11][12] Few methods have been published for its determination including thin layer chromatography which needs 2 h for tank saturation and can not determine lamotrigine in presence of its impurity, 5) gas chromatography, 13) capillary electrophoresis 14,15) and immunoassay. 16,17) In the present study we suggest a simple selective and validated spectrophotometric method using p-chloranilic acid which is used as chromogenic agent for different drugs, it gives an immediate purple chromogen at room temperature.18) Also TLC and HPLC methods that can identify and quantitate lamotrigine in presence of its impurity 2,3-dichlorobenzoic acid, in bulk and dosage form. ExperimentalInstrumentation Shimadzu UV/VIS spectrophotometer 1601. Shimadzu dual wave length flying spot densitomerter, Model CS-9301, photomodeϭreflection, scan modeϭzigzag and swing widthϭ10. TLC plates (10ϫ10 cm) aluminium plates precoated with 0.25 mm silica gel F254, were purchased from E. Merck. UV lamp-short wave length 254 nm. The HPLC system (Waters Co.) consisted of a Model 600 LC series pump and 600 controller unit, 486 tunable absorbance detector, an injector valve with a 20 ml constant loop, and 745 data module. A 250ϫ4.6 mm Alltech Adsorbosphere C 18 , 10 mm column was used for separation and quantification.Materials and Reagents Lamotrigine working standard, was supplied by Delta Pharma Co. (India), the purity of the sample was found to be 99.68Ϯ0.97% according to the reported specifications.3) 2,3-Dichlorobenzoic acid (99.90%), was purchased from Riedel-de Haem Pestanal. Lamictal tablets were purchased from Welcome Co. Egypt, labeled to contain 25 mg lamotrigine per tablet. p-Chloranilic acid (E. Merck ), 42 mg ml Ϫ1 in acetone. Methanol, acetonitrile and ethylacetate (Lab-scan, Ireland). Potassium orthophosphate (El-Nasr Co., Egypt). All chemicals are of spectroscopic and chromatographic grade.Standard Solutions Lamotrigine (1 mg ml Ϫ1) was prepared in acetone for spectrophotometric method, and in methanol for TLC and HPLC m...

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Lamotrigine analysis in blood and brain by high-performance liquid chromatography

Cited by 58 publications

References 38 publications

Population pharmacokinetics of lamotrigine in Chinese children with epilepsy

Population pharmacokinetics of lamotrigine in Chinese children with epilepsy

Enhanced brain delivery of lamotrigine with Pluronic® P123-based nanocarrier

Development and Validation of Spectrophotometric, TLC and HPLC Methods for the Determination of Lamotrigine in Presence of Its Impurity

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Lamotrigine analysis in blood and brain by high-performance liquid chromatography

Cited by 58 publications

References 38 publications

Population pharmacokinetics of lamotrigine in Chinese children with epilepsy

Population pharmacokinetics of lamotrigine in Chinese children with epilepsy

Enhanced brain delivery of lamotrigine with Pluronic&reg; P123-based nanocarrier

Development and Validation of Spectrophotometric, TLC and HPLC Methods for the Determination of Lamotrigine in Presence of Its Impurity

Contact Info

Product

Resources

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Enhanced brain delivery of lamotrigine with Pluronic® P123-based nanocarrier