A Current Analytical Review of Analytical Methods for
Edaravone
Bhumi K. Patel1*, Dr. Hasumati A. Raj1, Dr. Vinit C. Jain1, Priyanka S. Malani1, Hiral M.
Pokiya1
1
Shree Dhanvantary Collage of Pharmacy, Kim, Surat, Gujarat, India.
*Email: patelbhumi1912@yahoo.in
Address For correspondence:
Department of Quality Assurance
Shree Dhanvantary Pharmacy College
Near Railway Station, Kudsad Road.
At : Kim, Taluka : Olpad, Dist: Surat, Pin code : 394110
Mobile No : 9427461293
Number of figures : 1
Number of tables: 2
Abstract :
Edaravone is a Neuroprotective agent is available in the different pharmaceutical dosage forms,
generally in Parental Forms. The drug is used in memory disorders like Alzheimer’s disease,
Ischemic Stroke. This article reviews the current analytical methods for identification and
quantitative determination of Edaravone in samples. The clinical and pharmaceutical analysis of
Edaravone requires effective analytical procedures for quality control, Pharmacodynamics,
pharmacokinetic studies as well as stability study. An extensive survey of the literature published
in various analytical and pharmaceutical chemistry related journals has been conducted and the
instrumental analytical methods which were developed and used for determination of
Edaravone in bulk drugs, formulations and biological fluids have been reviewed. This review
covers the time period from 2002 to 2010 during many analytical methods including
spectrophotometric methods like Fluorescent Assay; and chromatographic method including
Residue by HPLC, HPTLC were reported. The application of these methods for the
determination of Edaravone in pharmaceutical formulations and biological samples had also been
discussed.
Keywords: Edaravone, Analytical Method, Chromatographic Method, Fluorescent Method
1. Introduction(1,2):
Edaravone is 5-methyl-2-phenyl-2,4-dihydro-3H-pyrazol-3-one is a pyrazole derivative
appears as white to off white crystalline powder (Figure 1). The drug is freely soluble in
Distilled Water. Edaravone is a weak base with pKa values of 7(3), Five-membered
Pyrazole Ring. Edaravone melts at 127-131 ºC.
Figure 1: Chemical Structures of Edaravone(1,2)
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-OHDAinduced dopaminergic neurotoxicity in the striatum and substantia nigra, 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
substantia nigra, though notably not to the striatum.(10-12)
The use of the Edaravone as a drug essential in pharmaceutical formulations highlights
the requirement for its determination and quantification with appropriate analytical
methods. This paper gives an overview of the analytical techniques that are available and
nowadays have been used for determination of Edaravone in pharmaceutical and
biological samples.
2. Combination of Edaravone
Edaravone had no comination with other drug.
3. Analytical Method
A. Compendial Method:
Edaravone is not official in Pharmacopoeia.
B. Reported Method:
i.
Fluorescent Method:
A Novel Fluorescent Assay for Edaravone with Aqueous Functional Cdse
Quantum Dots.
ii.
Drug
Method
Edaravone
Fluorescent Assay
Quantum
Dots
Aqueous
Functional
Cdse
Calibration Reference
range
1.45–17.42 13
μg/mL
Chromatographic Methods:
The high-pressure liquid chromatography (HPLC) for residue determination
HPTLC method are widely used chromatographic methods in the analysis of
Edaravone.
Summary of Chromatographic Method of Edaravone
Drug
Method
Edaravone RP-HPTLC
in Human
Plasma
Mobile phase
-
Stationary
phase
Pre
coated
RP-18 GF 254aluminum
Wave
Length
-
Reference
14
sheet
Residue in HPLC
edaravone
0.05mol/L ammonium Diamonsil
acetate - acetonitrile C18 column
(80∶20)
233nm
15
4. CONCLUSION
Presented systematic review covers the current analytical methods for the determination
of Edaravone in pharmaceutical and biological samples. The limitation of the reported
methods requires developing new optimized method which would be suitable for
intended analytical purpose for analyzing the content of Edaravone in pharmaceutical
and biological samples. The new trends and advances for quantification of Edaravone
are based on using high-pressure liquid chromatography and Spectroscopic Method
which are widely available and flexible method. There is not method based on the UV
analysis, so it is wide option for determination of Edaravone in Pharmaceutical
dosage form. The HPLC method could be automated; there are different column
fillings; different solvents with different polarity as mobile phases and different
detection modes. The faster time, high sensitivity, specificity and better separation
efficiency enable HPLC to be used frequently for the simultaneous qualitative and
quantitative determination of pyrazole derivatives in the comparison with the other
methods. The development of a new established method should reduce existing
analytical problems including many steps for the preparation of the sample, as well as
improving the resolution which can give accurate results for the concentration of all
Edaravone samples and could be used for routine analysis.
5. REFERENCE:
1) Edaravone Drug Info.(database available on internet):Chemical Book. Available
from: www.chemicalbook.com/ProductMSDSDetailCB1287462_EN.htm
2) Edaravone Drug Info.(database available on internet):Lookchem. Available from:
http://www.lookchem.com/Edaravone/
3) Toshiaki W, Munenori T, Satoru T. The Novel Antioxidant Edaravone: From
Bench to Bedside. Cardiovascular Therapeutics; 20098,26:101–114.
4) Doherty AM. Annual Reports in Medicinal Chemistry. Boston: Academic Press;
2002,37.
5) Watanabe T. et al. Research and development of the free radical scavenger
edaravone as a neuroprotectant. Yakugaku Zasshi (in Japanese); 2004,124(3):99–
111.
6) Higashi Y, Jitsuiki D, Chayama K, Yoshizumi M. Edaravone (3-methyl-1-phenyl2-pyrazolin-5-one), a novel free radical scavenger, for treatment of cardiovascular
diseases. Recent Patents on Cardiovascular Drug Discovery; 2006,1(1):85–93.
7) Yoshida H. et al. Neuroprotective effects of edaravone: a novel free radical
scavenger in cerebrovascular injury. CNS Drug Reviews;2006,12(1):9–20.
8) Yuan WJ. et al. Neuroprotective effects of edaravone-administration on 6-OHDAtreated dopaminergic neurons. BMC Neuroscience; 2008,9:75.
9) Kawasaki T. et al. Protective effect of the radical scavenger edaravone against
methamphetamine-induced dopaminergic neurotoxicity in mouse striatum.
European Journal of Pharmacology; 2006,542(1-3):92–99.
10) Kawasaki T. et al. Edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one), a radical
scavenger, prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine induced
neurotoxicity in the substantia nigra but not the striatum. The Journal of
Pharmacology and Experimental Therapeutics; 2007,322(1):274–281.
11) Yokoyama H. et al. Role of reactive nitrogen and reactive oxygen species against
MPTP neurotoxicity in mice. Journal of Neural Transmission; 2008,115(6):831–
842.
12) Yokoyama H. et al. Comparative pharmacological study of free radical scavenger,
nitric oxide synthase inhibitor, nitric oxide synthase activator and cyclooxygenase
inhibitor against MPTP neurotoxicity in mice. Metabolic Brain Disease;
2008,23(3):335–349.
13) Ping Liao, Zheng-Yu Yan, Zhi-Ji Xu, Xiao Sun. A novel fluorescent assay for
edaravone with aqueous functional CdSe quantum dots. Spectrochimica Acta Part
A: Molecular and Biomolecular Spectroscopy;2009,72(5):75
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In Vitro Estimation of Edaravone in Human Plasma. Indian Journal of
Pharmaceutical Science; 2010,72(2):276-282.
15) Li jin-lin et al. Determination of Phenylhydrazine Residues in Edaravone by
HPLC. Institute of Medical Information; CAMS, 2009.