The HPLC method for Armodafinil both bulk & in combination are given in Table 1 which includes parameters like matrix, stationary phase, mobile phase composition, detection wavelength RF value, retention time etc. HPTLC method reported in Table 2 includes parameter like matrix, stationary phase, mobile phase, RF, DL etc. The table 3 includes the GC-MS method for Armodafinil which involve the parameters like Matrix, stationary phase, mobile phase composition, Carrier gas, Retention time, flow rate etc. The table 4 includes the Capillary Electrophoresis method for Armodafinil which involve the parameters like Matrix, Capillaries wavelength, Separation Voltage, Temperature and pressure etc. Spectrometric methods for Armodafinil include UV-Visible Spectroscopy.

Armodafinil is the R-enantiomer of modafinil, a wake-promoting drug that predominantly affects brain areas involved in wakefulness control [1]. The US Food and Medicine Administration has licensed the drug for the treatment of individuals with excessive drowsiness caused by obstructive sleep apnea, narcolepsy, or shift work disorder [2]. The working mechanism is still a mystery. The dopamine transporter in the striatum and the norepinephrine transporter in the thalamus are both sensitive to modafinil [3]. Hypocretin, histamine, -adrenergic, -aminobutyric acid and/or glutamate receptors are all affected by modafinil [4]. 2-[(R)-(diphenylmethyl) sulfinyl] acetamide and 2-(R-benzhydrylsulfinyl) acetamide are the chemical names for armodafinil [5].

Armodafinil Pharmacodynamics:

Modafinil and its R-enantiomer, armodafinil, have uncertain therapeutic mechanisms in vivo [6]. Armodafinil inhibits dopamine re-uptake via binding to the dopamine transporter. It is not, however, a dopamine receptor agonist that acts directly or indirectly. In some animal brain regions, these binding inhibitory effects have been linked to higher extracellular dopamine levels [5]. Modafinil has complicated pharmacodynamic features since it interacts with a number of central pathways, including the catecholaminergic system. Both the R- and S-enantiomers bind to DAT35 and raise DA levels in many brain locations, including the prefrontal cortex (PCF), enhancing executive functions such as attention, impulse control, and memory [7].

Amodafinil pharmacokinetics:

Absorption: After numerous or a single oral administration, modafinil is absorbed at least 40 to 65 percent (oral bioavailability) and reaches maximum plasma concentrations (Cmax) 2–4 hours later. Because of its limited water solubility, it is not suitable for intravenous delivery in humans [7]. Oral administration of armodafinil causes rapid absorption, with peak plasma concentrations appearing in about 2 hours in the fasting condition. Food has no effect on armodafinil's overall bioavailability; however, the time to peak concentration can be delayed by 2–4 hours [5].

Distribution: Modafinil has a plasma protein binding of around60%, primarily to albumin, and an apparent volume of distribution of 0.8 L/kg following single or several oral doses, indicating that it can easily permeate tissues [7]. About 60% of modafinil is linked to plasma proteins, primarily albumin [8].

Metabolism: Modafinil is extensively degraded in the liver, largely via amide hydrolysis to form an acid metabolite, into inactive metabolites; ((±)2- [(diphenylmethyl) sulfinyl] acetic acid; modafinic acid) catalyzed by an esterase and/or amidase; ii) by S-oxidation via cytochrome CYP3A4 or CYP3A5 to produce a sulfone (2- [(diphenylmethyl) sulfanilyl] acetamide); iii) by aromatic ring hydroxylation; and iv) by glucuronide conjugation [7]. The principal metabolic process is amide hydrolysis, which does not require cytochrome P450 (CYP) activity. Cytochrome CYP3A4/5 plays a role in sulfone production [8].

Excretion: The elimination half-life is roughly 12–15 hours, owing to the kinetics of the R-enantiomer, as the S-enantiomer has a half-life of 4–5 hours [9]. Individuals with cirrhosis had a 60% reduction in modafinil clearance, while patients with chronic hepatic insufficiency have a doubled Cmax [10]. The main urinary metabolite, modafinil acid, accounts for 35 percent to 60 percent of the dosage [11].

Analytical accounts on Armodafinil:

The widespread literature survey exposed multiple analytical techniques like UV spectrophotometry method, HPLC, HPTLC, LC-MS/MS, for the determination of Armodafinil in bulk and pharmaceutical formulation. These reported methods describe the evaluation of armodafinil in various dosage forms like tablets and matrix like human plasma.

HPLC Method

P. Vivek Sagar et. al. outlined a stability showing RP HPLC method for the estimation of armodafinil in tablet dosage form. Chromatography was carried out using isocratic elution on a 4.6 x 250 mm stainless steel Hibar C18 column filled with octadecylsilane bound to porous silica (C18) with a particle size of 5 micron. The mobile phase is made up of 50:50 v/v acetonitrile and water. The effluent is measured at 220 nm and the flow rate is 1.0 ml/min. The retention time for armodafinil was 3.8 minutes [12].

Kambham Venkateswarlu et. al. given a validated stability indicating RP-HPLC method for estimation of Armodafinil in pharmaceutical dosage forms; also presented characterization of its base hydrolytic product. The separation was carried out on a C18 column with a 45:55 percent v/v combination of water and methanol as the mobile phase. At 1ml/min, eluents were identified at 220nm. Milder stress conditions were used first, followed by greater circumstances. For Armodafinil, the linearity of the suggested approach was tested in the range of 20-120g/ml. It was discovered that the retention time was 8.1 minutes [13].

Devi Ramesh et. al. performed an analytical approach for development and validation of new LC-MS/MS method for the determination of armodafinil in human plasma. Using 0.2 percent formic acid: methanol (15:85 v/v) as mobile phase on a hypurity advance C-18 column (5; 100 4.6 mm) at a flow rate of 1.0 ml/min, chromatographic separation was obtained in 3.0 minutes. The linearity of the drug concentration range of 50-10000 ng/mL was demonstrated (r2 = 0.9989) [14].

Ramisetti Nageswara Rao et. al. given an enantioselective HPLC resolution of synthetic intermediates of armodafinil and related substances; where armodafinil was studied on polysaccharide-based stationary phases, viz. cellulose tris-(3,5-dimethylphenylcarbamate) (Chiralcel OD-H) and amylose tris-(3,5-dimethylphenylcarbamate) (Chiralpak AD-H) by HPLC. When comparing the cellulose-based Chiralcel OD-H column to the amylose-based Chiralpak AD-H column, a satisfactory separation was achieved. A mobile phase containing n-hexane–ethanol–TFA (75:25:0.15 v/v/v) was used to achieve baseline separation with Rs A1.38. At 225 nm, a photodiode array detector was used to detect the enantiomers, while a polarimetric detector was used to identify the enantiomers [15].

CN Prathyusha Naik et. al. performed stability indicating assay method of armodafinil. The C8 (250 x 4.6 mm, 5m) column was used to separate the mobile phase of water and methanol (10 percent v/v OPA) 55:45 percent v/v. At 1ml/min, eluents were identified at 225 nm. Stress tests were carried out utilising acid, base, oxidizing agents, light, and heat to achieve a 10-20

UV-Visible Spectroscopy Method:

Tejaswi Jonnalagadda et. al. reported a simple visible spectrophotometric method for the determination of armodafinil in bulk and pharmaceutical dosage form. In the range of 10- 50 g/ml, the drug follows Beer Lambert law, with a correlation coefficient of 0.999. Armodafinil's percentage recovery in pharmaceutical dosage form is between 96 and 106 percent. The oxidative coupling reaction of 3-methyl-2-benzathiazoline hydrazone (MBTH) in the presence of ferric chloride is the basis for this approach (Fecl3). With the solvent system methanol: water, an absorption-maxima were discovered at 596nm [29].

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