INTRODUCTION:

Lamotrigine is chemically 6-(2,3-dichlorophenyl)1,2,4-triazine-3,5-diamine. Lamotrigine is an anticonvulsant drug which is used in the treatment of epilepsy and bipolar disorder. For epilepsy it is used to treat the partial seizures, primary and secondary tonic-clonic seizures, and seizures associated with the Lennox-Gastaut syndrome and are chemically unrelated to other anticonvulsants (due to Lamotrigine being a Phenyltriazine). Lamotrigine has relatively few side-effects and it does not require blood monitoring in monotherapy. Lamotrigine also acts as a mood stabilizer. It is an Antiepileptic drug (AED) of the phenyltriazine Class^1,2. It is the first medicament since lithium approved by food and drug administration (FDA) for the maintenance and the treatment of bipolar type I disorder. Chemically it is unrelated to other anticonvulsants, lamotrigine has relatively few side-effects and does not require blood monitoring^3,4,5

Table No.1: Drug profile of Lamotrigine

Drug name	Lamotrigine.
Drug category	Anti-epileptic agent.
Chemical formula	C₉H₇Cl₂N₅
IUPAC name	6-(2,3-dichlorophenyl)-1,2,4-triazine-3,5-diamine
Molecular weight	256.091gm/mol.
Melting point	220^oC.
Half life	24 to 35 hrs.
Chemical structure	Fig 1. Chemical structure of Lamotrigine
BCS Class	Class-II(Low solubility and High permeability)
Solubility	Very slightly soluble in water,Ethanol,0.1M HCL, DMSO(Dimethylsulfoxide), Dimethyl formamide(DMF).

Analytical Methods used for the Determination of Lamotrigine:

1) High performance liquid chromatography (HPLC):

In the field of analytical chemistry high performance liquid chromatography (HPLC) is taken into account by several to be most exciting and dynamic technique of past decade. The typical HPLC separation relies on the selective distribution of analytes between a liquid mobile phase and in an immiscible stationary phase. The sample is 1st introduced by the means that of an injection port into the mobile phase stream that’s delivered by a high-pressure pump. Next, the components/elements of this sample mixture are separated on the column, a process monitored with a flow-through detector as because the isolated components/elements emerge from the column. HPLC columns are mainly created up by packing the column with the spherical silica gel beads that are created with hydrophobic stationary phase. The common stationary phases are C4(butyl), C8(octyl), C18(octadecyl), phenyl (phenyl propyl) and nitrile (cyanopropyl) columns^6,7,8,9

Table No.2: Summary of RP-HPLC method for determination of Lamotrigine

Sr No.	Drug	Method	Description	Reference
1.	Lamotrigine	RP-HPLC	Column: Fortis C18 Mobile phase: Acetonitrile: Phosphate buffer (40:60v/v) Flow rate: 1ml/min Retention time: 5.1min	10
2.	Lamotrigine	RP-HPLC	Column: ACE-5 C18 Mobile phase: Methanol: Acetonitrile:0.01M Potassium Phosphate Monobasic (30:15:55, v/v/v) Flow rate: 1ml/min Retention time: 6.8 & 6.2	11
3.	Lamotrigine	HPLC	Column: Zorbax SB-C18 Mobole phase: Water and Methanol (35:65 v/v) Flow rate: 0.700ml/min Retention time: 10.39min	12
4.	Lamotrigine	HPLC	Column: Eclipse XDB-C18 Mobile phase: potassium dihydrogen orthophosphate buffer and methanol (65:35v/v) Flow rate: 0.8ml/min Retention time: 10min	13
5.	Lamotrigine	RP-HPLC	Column: Luna C18 Mobile phase: potassium dihydrogen phosphate buffer and methanol (60:40v/v) Flow rate:1.0ml/min Retention time: 6.1min	14
6.	Lamotrigine	RP-HPLC	Column: Symmetry C18 Mobile phase: Acetonitrile and potassium dihydrogen phosphate (60: 40v/v) Flow rate: 0.7ml/min Retention time: 2.797min	15
7.	Lamotrigine	RP-HPLC	Column: LiChrospher RP-18 Mobile phase: Methanol: Acetonitrile: 15 mM phosphate buffer (pH 2.5) (40:30:30% v/v/v) Flow rate: 1ml/min Retention time: 3.4min	16
8.	Lamotrigine	RP-HPLC	Column: RESTEK C18 Mobile phase: Acetonitrile and water (55:45v/v) Flow rate: 1ml/min Retention time: 4.4min	17
9.	Lamotrigine	RP-HPLC	Column: Xterra C18 Mobole phase: Methanol and potassium dihydrogen phosphate (50:50v/v) Flow rate: 0.8ml/min Retentionntime: 3.8min	18
10.	Lamotrigine	RP-HPLC	Column: BDS Hypersil C18 Mobile phase: potassium dihydrogen phosphate and acetonitrile (60:40v/v) Flow rate: 1.0ml/min Retention time: 10min	19
11.	Lamotrigine	HPLC	Column: SymmetryC18 Mobile phase: potassium dihydrogen phosphate and acetonitrile (60:40v/v) Flow rate: 0.7ml/min Retention time: 2.797min	20
12.	Lamotrigine	RP-HPLC	Column: Hypersil ODS C18 Mobile phase: methanol: 0.01 mol. L-1 TBAHS (Tetra butyl ammonium hydrogen sulphate) (50:50 % v/v)	21
13.	Lamotrigine	HPLC	Column: C18 Mobile phase: Methanol and phosphate buffer(70:30v/v) Flow rate: 1.1ml/min Retention time: 10min	22
14.	Lamotrigine	RP-HPLC	Column: Supelco C18 Mobile phase: Methanol and potassium dihydrogen orthophosphate (65:35v/v) Flow rate:1ml/min Retention time: 3.7min	23
15.	Lamotrigine	HPLC-UV	Column: Acclaim C18 Thermo Mobile phase: methanol and potassium dihydrogen phosphate (50:50v/v) Flow rate: 1.0ml/min Wavelength: 210nm	24

2) UV Spectroscopy Method:

The UV spectroscopy is an crucial tool in an analytical chemistry. It is also called as Electronic Spectroscopy because it involves the proportion of the electrons from the ground state to the excited state. UV spectroscopy is a type of absorption spectroscopy in which light of the ultra-violet region (200-400nm) is absorbed by the molecule. Absorption of the ultra-violet radiations leads to the excitation of the electrons from the ground state to the higher energy state.^25,26,27

Principle of UV Spectroscopy:

UV Spectroscopy mainly obeys the Beer-Lambert Law, which states that, When a beam of an a monochromatic light is passed through a solution of an absorbing substance, the rate of decrease of the intensity of radiation with thickness of the absorbing solution is proportional to the incident radiation as well as the concentration of the solution.^28,29

Instrumentation requisite for measure of UV visible spectroscopic radiations mainly consists of Light source, i.e., Tungsten filament lamps and Hydrogen-Deuterium lamps that are most widely used and are suitable light source as they cover the whole UV region^30,31. Monochromators are generally composed of the prism and slits. Most of the spectrophotometers which are double beam spectrophotometers. Sample and reference cells is one of the 2 divided beams is passed through the sample solution and the second beam is passed through the reference solution, both the sample and reference solution are contained in the cells^32,33. Detector typically they’re the 2 photocells serve the purpose of detector in UV Spectroscopy, in it one of the photocell receives the beam from the sample cell and the second detector receives the beam from the reference³⁴. Amplifier, in it the alternating current generated in the photocells is transferred to the amplifier. An amplifier is coupled to a small servometer. Recording devices, most of the amplifier is coupled to a pen recorder that is connected to the pc, it stores all the information generated and produces the spectrum of the required compound³⁵.

Applications of UV spectroscopy are, to detect the functional group, detection of extent of conjugation, to identify the molecular compound, determine the configuration of geometrical isomers, and to determine the purity of the substance.³⁶.

Mainly the absorption and the intensity shift in the UV Spectroscopic methods are, Bathochromic effect, Hypochromic, Hyperchromic and Hypochromic effects respectively.³⁷

Table No. 3: Summary of UV Spectroscopic methods for Determination of Lamotrigine.

Sr No.	Drug	Method	Description	Reference
1.	Lamotrigine	UV-Visible Spectrophotometric Method	Wavelength: 610nm Solvent: LMT solution Linearity: 0.2-0.3µg/mL	38
2.	Lamotrigine	UV-Visible Spectrophotometric Method	Wavelength: 307nm Solvent: 0.1M NaOH Linearity: 5-50 mcg/ml	39
3.	Lamotrigine	UV-Visible Spectrophotometric Method	Wavelength: 519nm Solvent: p-chloranilic acid Linearity: 10-200µg/ml	40
4.	Lamotrigine	UV-Visible Spectrophotometric Method	Wavelength: 374nm Solvent: tetracyanoquinodimethane Linearity: 3.0-18µg/ml	41
5.	Lamotrigine	UV-Visible Spectrophotometric Method	Wavelength: 304nm Solvent: Water Linearity: 0.01-0.2µg.mL-1	42
6.	Lamotrigine	UV-Visible Spectrophotometric Method	Wavelength: 410nm Solvent: Ethanol Linearity: 2.0-20µg/ml	43
7.	Lamotrigine	UV-Visible Spectrophotometric Method	Wavelength: 403nm Solvent: Water Linearity: 50-350µg/ml	44
8.	Lamotrigine	UV-Visible Spectrophotometric Method	Wavelength: 413nm Solvent: Methanol Linearity: 0.5-12µg/ml	45

3) Stability Indicating Method:

The main purpose of stability studies is to contribute the authentication on how the quality of an drug substance or a drug product alters within a time under the influence of a variety of environmental factors embody such as, temperature, humidity, light, and to establish a re-test period of an drug substance of a shelf-life of the drug formulation.

Stability testing of the pharmaceutical products is an complex set of procedures which mainly involves, the considerable cost, time consumption & scientific expertise in order to develop an quality, efficacy and safety of an drug formulation.

Most important factors during the developmental stages includes, pharmaceutical analysis and stability studies which are mainly required to determination and assurance of the identity, potency and purity of the ingredients^46,47

Table No.4:- Summary of Stability Indicating methods for determination of Lamotrigine

Sr No.	Drug	Method	Description	Reference
1.	Lamotrigine	RP-HPLC	Column: Thermo C18 Mobile phase: Flow rate: 1.0ml/min Retention time: 5.013min Wavelength: 225nm	48
2.	Lamotrigine	HPLC	Column: Phenomenax C18 Mobile phase: methanol and ammonium buffer (50:50v/v) Flow rate: 0.8ml/min Wavelength: 225nm	49
3.	Lamotrigine	UPLC	Column: BEH C18 Mobile phase: potassium dihydrogen phosphate buffer, methanol and acetonitrile (40:60v/v) Wavelength: 228nm Linearity: 1.0-75µg/ml	50
4.	Lamotrigine	RP-UPLC	Column: Symmetry C18 Mobile phase: potassium dihydrogen phosphate buffer and acetonitrile (40:60v/v) Retention time: 1.5min Wavelength: 215nm Linearity: 2.0-10.0µg/ml	51

CONCLUSION:

So, from the above information it should be concluded that the various analytical methods which were used for the determination of Lamotrigine alone or in combination has been successfully used on a routine basis and allows the quantification of the drug in various pharmaceutical dosage forms. These all methods are simple, fast, accurate, sensitive, reproducible and possess excellent linearity and precision characteristic.

ACKNOWLEDGEMENT:

I would like to express my sincere thanks to Dr. Suhas Siddheshwar and Prof. Mahesh H Kolhe for their valuable guidance and support for this review work.

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Received on 17.05.2021 Modified on 07.06.2021

Research J. Science and Tech. 2021; 13(3):229-234.

DOI: 10.52711/2349-2988.2021.00036