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EDARAVONE: A REVIEW ON ANALYTICAL METHOD AND ITS DETERMINATION IN BIOLOGICAL MATRIX AND SYNTHETIC MIXTURE

 

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ABOUT AUTHORS:
Patel Divya .A.1*, Raj.Hasumati1, Patel Roshni2
1Department of Quality Assurance, Shree Dhanvantary Pharmacy College, Kim, Surat, Gujarat
2Piooner College of pharmacy, Baroda, Gujarat
*divyapatel388@gmail.com

ABSTRACT
Edaravone is a potent free radical scavenger (antioxidant) mainly use in the form of injection. It is used in the treatment of various cardiovascular diseases like acute ischemic stroke as well as in gastrointestinal injuries. This review article represent the various analytical methods which has been reported for estimation of edaravone in biological matrix as well as in synthetic mixture.The spectrophotometric techniques like fluorescent assay and ratio derivative spectroscopy; Chromatogrraphic methods like HPLC, HPTLC and RP HPLC were reported.

INTRODUCTION(1,2):
Edaravone is 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one is apyrazole derivative appears as white to off white crystalline powder. The drug is freely soluble in Distilled Water. solubility in water is 3 g/1 L. Edaravone is a weak base with pKa values of 7(3), Five-membered Pyrazole Ring. Edaravone melts at 127-131 ºC. Boils at 287º C.


MECHANISM OF ACTION(3):
Edaravone has been reported to exert antioxidant effects because it can quench hydroxyl radicals and hydroxyl radical-dependent lipid peroxidation. Edaravone reduces elevated levels of hydroxyl radicals and superoxide radicals in several models of ischemia. In early studies of antioxidant activity of edaravone, its pKa was found to be 7.0, and the rate of oxidation for edaravone was positively correlated with pH. The putative mechanism underlying the antioxidant action of edaravone is electron transfer from an edaravone anion to peroxyl radical, and this reaction breaks the chain oxidation of lipids.

Edaravone is excreted as unmetabolized drug (~1%) or metabolized by sulfation (5–13%) or glucuronidation (68–83%) and excreted in urine within 24hours of administration.


Edaravone is a neuroprotective agent used for aiding neurological recovery following acute brain ischemia and subsequent cerebral infarction.(4) It acts as a potent antioxidant and strongly scavenges free radicals, protecting against oxidative stress and neuronal apoptosis.(5-7)Edaravone has been shown to attenuate methamphetamine- and 6-OHDA-induced dopaminergic neurotoxicity in the striatum and substantianigra, and does not affect methamphetamine-induced dopamine release or hyperthermia.(8,9) It has also been demonstrated to protect against MPTP-mediated dopaminergic neurotoxicity to the substantianigra, though notably not to the striatum.(10-12)

Combination of edaravone(13)
Edaravone+ozagrel
Edaravone+alteplase (tPA)
Edaravone +citicholine sodium

Marketed formulation of edaravone(13)
Radicut®,Radicut bag

1.Analytical Method
A. CompendialMethod:
Edaravone is not official in Pharmacopoeia.

B. Reported Method:
I.
Fluorescent Method: A Novel Fluorescent Assay for Edaravone with Aqueous Functional Cdse Quantum Dots.

Table No.1: Summary of Fluorescent methodfor edaravone(14)

Drug

Method

Quantum Dots

Calibration range

Edaravone

Fluorescent Assay

Aqueous Functional Cdse

1.45–17.42 μg/mL

II. Chromatographic Methods:
The high-pressure liquid chromatography (HPLC)for residue determination. HPTLC method are widely used chromatographic methods in the analysis of Edaravone in plasma. RP HPLC method also developed for determination of concentration of edaravone in human serum and also for simultaneous determination of edaravone and citicoline sodium.

Table No.2: Summary of Chromatographic Method of Edaravone

Title

Method

Mobile phase

Stationary phase

Wave Length

Reference

Invitro estimation of Edaravonein Human Plasma

RP-HPTLC

-

Pre coated RP-18 GF254­aluminum sheet

-

15

Determination of phenyl hydrazine Residue in edaravone

HPLC

0.05mol/L ammonium acetate - acetonitrile (80:20)

Diamonsil C18 column

233nm

16

Determinationof edaravone and its related substance

HPLC

1%acetic acid :methanol

(40:60)

Hypersil -ODC18 column

243 nm

17

Estimate Conc,ofedaravone in human serum

RP HPLC

H3PO4 :Methanol

(50:50)

Hypersil C18 column

240 nm

18

III. UV spectroscopic method
First order derivative spectroscopy and Ratio derivative spectroscopic technique was developed for simultaneous determination of edaravone and citicolin sodium.

The ratio derivative spectroscopy method is based on dividing the spectrum for a mixture in to standard spectra for each of analysis and to obtain a spectrum that is independent of analyte concentration used as devisor.

Table No.3:Summary of UV spectroscopic method

Title

Method

Zero crossing point for edaravone

Zero crossing point for citicoline sodium

R2

REF.

Simultaneous estimation of Edaravone and citicoline sodium in synthetic mixture

Ratio derivative spectroscopic method

258.40

267 nm

0.999

 

0.999

19

Simultaneous estimation of Edaravone and citicoline sodium in synthetic mixture

First order derivative spectroscopic method

245.60 nm

271.20 nm

0.9996

 

0.9996

19

Table No.4:RP HPLC Method for simultaneous estimation of edaravone and citicoline sodium

Title

Method

Mobile phase

Stationary phase

Wave length

Ref.

Simultaneous estimation of edaravone and citicoline sodium in synthetic mixture

 RP HPLC

Acetonitrile and water

(70:30)

Phenomenexluna®

244 nm

20

DISCUSSION
Presented systematic review covers the current analytical methods for the determination of Edaravone and its combination in pharmaceutical and biological samples like serum and plasma. HPLC method were found to be most widely use for edaravone. Various chromatographic conditions are presented in table.

CONCLUSION
The sensitivity, specificity, and better separation efficiency enable HPLC to be used frequently for simultaneous qualitative and quantitative determination of edaravone. The presented information is useful for the future study for researcher involved in formulation development and quality control of edaravone.

REFERENCES:
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2)Edaravone Drug Info.(database available on internet):Lookchem. Available from: lookchem.com/Edaravone/
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4)Doherty AM. Annual Reports in Medicinal Chemistry. Boston: Academic Press; 2002, 37.
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14)Ping Liao, Zheng-Yu Yan, Zhi-JiXu, Xiao Sun. A novel fluorescent assay for edaravone with aqueous functional CdSe quantum dots. SpectrochimicaActa Part A: Molecular and Biomolecular Spectroscopy; 2009, 72(5):75
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16)Li jin-linet al. Determination of Phenylhydrazine Residues in Edaravone by HPLC. Institute of Medical Information; CAMS, 2009.
17)Fu Gui-Ying, WEN Ming-Ling, JIA Li-Hua,ZUOXiu-Ping, Determination of content and related substance of edaravone injection by HPLC.; Pharmaceutical Journal Of Chinese people´s Liberation Army.2009-02.101-14
18)WEI Min, XIAO Yi (Guangxi Liuzhou Municipal People´s Hospital, China), Determination of concentration of edaravone in human serum by RP HPLC; Clinical pharmacy 2007-08.142-143
19)Bhumi K.Patel, Hasumati A.Raj, Vineet C.Jain, Simultaneous Estimation of Edaravone and Citicoline sodium by Ratio derivative spectroscopic method in synthetic mixture,; Pharmascience Monitor, An International Journal Of Pharmaceutical Science, 5(2)sup-1 Apr-June 2014,:118-128.
20)Bhumi K Patel, Hasumati A Raj, Vineet C Jain, Vishnu Sutariya, Mihir Bhatt, Kaushik Patel, method development and validation of RP HPLC for simultaneous estimation of edaravone and citicoline sodium in synthetic mixture, inventi rapid: pharm analysis & quality assurance publication date: 2014/5/6.

REFERENCE ID: PHARMATUTOR-ART-2257

PharmaTutor (ISSN: 2347 - 7881)

Volume 2, Issue 10

Received On: 31/07/2014; Accepted On: 10/08/2014; Published On: 01/10/2014

How to cite this article: DA Patel, R Hasumati, R Patel; Edaravone: A Review on Analytical Method and its Determination in Biological Matrix and Synthetic Mixture; PharmaTutor; 2014; 2(10); 80-84

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