A Review: Determination of Clopidogrel Bisulphate in Biological Fluid and Pharmaceutical Dosage Forms

Pankaj Savani¹*, Vineet Jain², Hasumati Raj¹, Sagar Patel¹

¹Department of Quality Assurance, Shree Dhanvantary Pharmacy College, Kim, Dist: Surat, Gujarat, India. 394110

²Department of Pharmacognosy, Shree Dhanvantary Pharmacy College, Kim, Dist: Surat, Gujarat, India. 394110

*Corresponding Author E-mail: pankajsavani75@gmail.com

ABSTRACT:

Clopidogrel Bisulphate is a mainly use in Anti platelet agent as a ADP receptor blocker and administration of oral tablet dosage form. Chemically, it is Methyl 2-(2- Chlorophenyl) -2-(6, 7-dihydro thieno [3,2-C] Pyridine-5(4H)-yl) Acetate sulphate. It is used in the treatment of various cardiovascular diseases like Ischemic stroke as well as in Glomerular inflammation, Myocardial infarction, Atherosclerosis disease, Unstable Angina. 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 as single or combination with other drugs in bulk drugs, formulations and biological fluids have been reviewed. These reviews of analytical methods including Spectrophotometric methods like Spectrophotometry, Chromatographic method including HPLC, HPTLC were reported.

KEYWORDS: Clopidogrel Bisulphate, Analytical methods, Compendial Method, UV Spectroscopic method, Chromatographic methods.

INTRODUCTION:

Clopidogrel Bisulphate is Methyl 2-(2- Chlorophenyl) -2-(6, 7-dihydro thieno [3,2-C] Pyridine-5(4H)-yl) Acetate sulphate is a novel and unique ADP receptor blockers. ^[1]

Figure 1: Chemical structure of Clopidogrel Bisulphate

Table 1 Drug Profile ^[2-3]

PARAMETERS	DESCRIPTION
Category	Anti-Platelet agent
Chemical formula	C16H16ClNO2S·H2SO4
IUPAC Name	Methyl 2- (2- Chlorophenyl) -2- (6,7- dihydro thieno [3.2-C] Pyridine- 5 (4H)-yl) Acetate sulphate
Molecular Weight	419.90 gm/mol
Characteristic	White Crystalline Powder
Solubility	Soluble in Methanol, Acetonitrile, DMSO and Ethyl acetate

MECHANISM OF ACTION:^[4]

Clopidogrel Bisulphate acts by inhibiting the ADP receptor on platelet cell membranes. It is a Prodrug, which requires CYP2C19 for its activation. The drug specifically and irreversibly inhibits the P2Y₁₂ subtype of ADP receptor, which is important in activation of platelets and eventual cross-linking by the protein fibrin. In Clopidogrel Bisulphate is fibrinogen Thienopyridine surface receptor on platelets is inhibits selective irreversible P2Y₁₂ Purinergic Receptor and also inhibits of ADP as fibrinogen induced platelet aggregation. So that inhibition of Adenylyl cyclase and reduced the inflammation, Ischemic stroke, Myocardial infarction, Atherosclerosis disease, Unstable Angina.

PHARMACOLOGICAL ACTION:^[5]

The platelet is integral to the initiation of thrombosis. Antiplatelet Drugs that affect platelet function are a fundamental part of primary and secondary management of atherosclerotic thrombotic disease. That indications for the use of Antiplatelet drugs in the management of thrombotic diseases include stroke, acute myocardial infarction (AMI), acute coronary syndrome (ACS), angina, percutaneous coronary intervention (PCI), cardiac surgery, primary and secondary cardiovascular disease prevention, peripheral vascular disease and thrombotic disorders such as A trial fibrillation. The risk versus benefit assessment of continuing or discontinuing these drugs should be made bearing in mind the proposed surgery and its inherent risk for bleeding or thrombotic complications as well as decisions relating to appropriate use of general or some form of regional anesthesia.

Figure 2: Mechanism of action Clopidogrel Bisulphate⁵

MARKETED FORMULATION OF CLOPIDOGREL BISULPHATE

Table 3 Marketed formulation of Clopidogrel Bisulphate

SR NO.	BRAND NAME	COMPANY NAME	FORMULATION	DOSE (mg)
1	Clopid	Hetero Drugs Ltd	Tablet	75
2	Clodrel	Unichem laboratories Ltd.	Tablet	75, 150
3	Clopivas	Cipla Ltd.	Tablet	75, 150
4	Clopicard	Okasa pharma Pvt. Ltd.	Tablet	75

ANALYTICAL METHODS:

This all are the methods which are used for the determination of Clopidogrel Bisulphate in marketed formulation and in biological fluids. This all analytical methods are reported which are seen during the literature survey. This article describes the review on the all reported analytical methods with specific conditions.

A. COMPENDIALMETHOD:

Clopidogrel bisulphate is high performance liquid chromatographic official method available in Indian pharmacopeia and united state pharmacopeia.

B. REPORTED METHOD:

1. UV SPECTROSCOPIC METHOD:

Spectrophotometric method is versatile and economical particularly for developing countries. Spectro photometric method has several advantages such as being easy, less expensive and less time consuming compared with most of the other methods. A simple, precise and economical Spectrophotometric method for the estimation of Clopidogrel Bisulphate in pharmaceutical bulk and tablet dosage form was developed and validated. Various methods like Q-absorption ratio, Simultaneous equation and Derivative methods are used for determination of Clopidogrel bisulphate alone or in combination with other drugs in marketed formulation. Below in table describes the various Spectroscopic methods with the method description and condition which are reported on review literature.

Table 4: Compendial method for Clopidogrel Bisulphate

Compendia	Method	Column	Mobile phase	Detection wavelength	Flow rate (ml/min)
IP^[6]	HPLC	C18 (15 cm x 4.6 mm, 5µ)	Potassium Phosphate buffer (pH-7.0) : Acetonitrile (75:25 v/v)	220 nm	1.0
USP^[7]	HPLC	C18 (15 cm x 4.6 mm, 5µ)	Potassium Phosphate buffer (pH-7.0) : Acetonitrile (75:25 v/v)	220 nm	1.0

Table 5: Summary of UV-Spectroscopic method for Clopidogrel Bisulphate

Title	Method	Solvent	λmax (nm)	Ref.
Development and Validation of Derivative UV-Spectrophotometric Methods for Quantitative Estimation of Clopidogrel in Bulk and Pharmaceutical Dosage Form	Derivative Spectroscopy	0.1 N HCl	219	8
Development and Validation of Spectrophotometric Method for Clopidogrel Bisulphate in pure and in film coated tablet dosage form	Simple UV-Spectroscopy method	Distilled water	222	9
Stability indicating Spectrophotometric method for Development and Validation of Clopidogrel Bisulphate tablet dosage form	Stability indicating Spectrophotometric method	Acetonitrile	220	10

Table 6 Summary of Chromatographic method for Clopidogrel Bisulphate

Title	Method	Stationary phase	Mobile phase	Detection wavelength (nm)	Ref.
Validation of assay for bulk Clopidogrel and for some tablet forms by Reverse-Phase High-Performance liquid chromatography	RP-HPLC	Develosil ODS HG-5 RP C18 (15 cm × 4.6 mm, 5 µm)	Acetonitrile : phosphate (65:35 v/v) buffer (pH 2.85)	225	11
Development and Validation of RP-HPLC method for the estimation of Clopidogrel Bisulphate	RP-HPLC	Hypersil BDS C18 (250 mm × 4.6 mm, 5 μm)	Potassium dihydrogen orthophosphate buffer: Acetonitrile in a ratio of (32:68 v/v) (pH 4.0)	220	12
Method Development and Validation of Clopidogrel Bisulphate by RP-HPLC in Bulk and Pharmaceutical dosage forms	RP-HPLC	Hypersil BDS C18 column (150 mm x 4.5 mm, 5 µm)	Acetonitrile : Phosphate buffer (pH: 3.0) in the ratio of 60:40 %v/v	224	13

Table 7 Summary of Spectroscopic method for Clopidogrel Bisulphate and its combination

Title	Method	Wave- length for Clopidogrel Bisulphate	Wave- length for other drug	Solvent	Ref
Quantitative Analysis for Clopidogrel Bisulphate and Aspirin by Second Derivative Spectrophotometric Method in Pharmaceutical preparation	2^nd Derivative Spectrophotometric Method	254 nm	216 nm	Methanol	14
Simultaneous estimation of Rosuvastatin Calcium and Clopidogrel Bisulphate in combined pharmaceutical formulation	Simple UV-Spectroscopy method	246 nm	250.4 nm	Water	15
Development and validation of UV-Spectrophotometric methods for simultaneous estimation of Amlodipine Besylate and Clopidogrel Bisulphate in bulk and tablet dosage form	Simple UV-Spectroscopy method	270 nm	360 nm	Methanol	16

Table 8 Summary of Chromatographic method for Clopidogrel Bisulphate and its combination

Title	Method	Stationary phase	Mobile phase	Detection wavelength (nm)	Ref.
Development and validation of RP-HPLC-UV method for simultaneous Quantitation of Clopidogrel bisulphate and Aspirin in bulk drug	RP-HPLC	Phenomenex Luna C18 column (250 mm × 4.6 mm, 5 µm)	0.3%ortho phosphoric acid (v/v) : Acetonitrile (40:60 v/v)	226	17
Bio-analytical determination of Clopidogrel and Pantoprazole by RP-HPLC method in rat plasma: Application to drug interaction study	RP-HPLC	C8 column (250 mm × 4.6 mm, 5 μm)	Potassium dihydrogen ortho phosphate buffer (pH -3.0) : Acetonitrile (40:60 v/v)	240	18
Simultaneous Determination of Clopidogrel and Pioglitazone by high performance liquid chromatography in bulk drug and dosage forms	HPLC	Inertsil ODS C18 column (250 mm × 4.6 mm, 5 μm)	Methanol : Acetonitrile : Water (80:10:10 v/v)	230	19

Table 9 Other Chromatographic method for Clopidogrel Bisulphate

Title	Method	Stationary phase	Mobile phase	Detection wave-length	Ref.
A Validated Stability Indicating HPTLC Method for Determination of Aspirin and Clopidogrel Bisulphate in Combined Dosage Form	HPTLC	Silica gel 60 F254	Carbon tetrachloride : Acetone (6:2.4 v/v)	220 nm	20
Determination of Clopidogrel Carboxylic Acid in Human Plasma by LC-MS/MS	LC-MS/MS	Symmetry C18 column (75 mm × 4.6 mm, 3.5μm)	Methanol: De-ionized water : Formic acid (75:25:0.1 v/v/v)	-	21
A novel GC-MS for the determination of Clopidogrel bisulphate in bulk and pharmaceutical dosage forms	GC-MS	META-5X column (30.0 m × 0.32 mm × 0.25 mm)	-	-	22

2. CHROMATOGRAPHIC METHOD:

Various chromatographic methods are used for the determination of the Clopidogrel Bisulphate alone or combination with other drugs in various marketed formulation and in biological fluids like human plasma. Chromatographic methods like Reverse phase High performance liquid chromatography (RP-HPLC) and High performance thin layer chromatography (HPTLC) are used for determination of Clopidogrel Bisulphate. Below in table describes the summary of the various chromatographic methods are used with the method description.

CONCLUSION:

The presented review highlights on various analytical methods reported on Clopidogrel Bisulphate and its combination with other drug. HPLC-HPTLC-UV methods were found to be most widely used. Various chromatographic conditions are presented in under Table. The faster time, high sensitivity, specificity and better separation efficiency enable HPLC to be used frequently for the determination of Clopidogrel Bisulphate in the comparison with the other methods. Other methods are also useful. In this way various analytical methods for the estimation of Clopidogrel Bisulphate in bulk or in various matrixes like plasma, alone or in combination with other drugs is discussed. The presented information is useful for the researchers especially those involved in the formulation development and quality control of Clopidogrel Bisulphate in combination with other drug.

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Received on 06.01.2016 Modified on 27.01.2016

Accepted on 07.02.2016 ©A&V Publications All right reserved

Res. J. Pharm. Dosage Form. & Tech. 8(1): Jan.-Mar. 2016; Page 66-70

DOI: 10.5958/0975-4377.2016.00009.4