CLOPIDOGREL BISULPHATE

Clopidogrel Bisulphate is used as an antithrombotic.
Clopidogrel Bisulphate is used an irreversible inhibitor of P2Y12.
Clopidogrel Bisulphate is an oral, thienopyridine class antiplatelet agent used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease.

CAS Number: 120202‑66‑6 
EC Number: 686‑767‑8 
MDL Number:MFCD00876395
Molecular Formula: C₁₆H₁₆ClNO₂S·H₂SO₄
Molecular Weight: ~419.9 g/mol 

SYNONYMS:
CLOPIDOGREL BISULPHATE, Clopidogrel hydrogen sulfate, Clopidogrel sulfate, CLOPIDOGREL SULFATE, CLOPIDOGREL HYDROGEN SULPHATE, Plavix, Stroka, opidog, Iscover, Myogrel, SR‑25990C, Clopidogrel bisulfate, Clopidogrel hydrogen sulfate, Clopidogrel sulfate, Clopidogrel hydrogen sulphate, CLOPIDOGREL BISULPHATE, CLOPIDOGREL SULFATE, Plavix, Stroka, opidog, Iscover, Myogrel, SR‑25990C, Thieno[3,2-c]pyridine-5(4H)-acetic acid,alpha-(2-chlorophenyl)-6,7-dihydro-,methyl ester,(alphaS)-,sulfate, (S)-Methyl (2-chlorophenyl)(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)acetate hydrogensulfate, CLP, (S)-Methyl (2-chlorophenyl)(6,7-dihydro-4H-thieno[3,2-c]pyridin-5-yl)acetate hydrogensulfate, CLOPIDOGREL BISULPHATE, Clopidogrel hydrogen sulfate, PLAVIX, CLOPIDOGREL SULFATE, CLOPIDOGREL HYDROGEN SULPHATE, Stroka, opidog, Myogrel, Iscover, SR-25990C

Clopidogrel Bisulphate is an antiplatelet agent.
Specifically, Clopidogrel Bisulphate inhibits the binding of ADP to its receptors on the membranes of platelet cells, and blocks ADP-mediated activation of the glycoprotein GPIIb/IIIa complex.

Clopidogrel Bisulphate is provided as delivered and specified by the issuing Pharmacopoeia.
All information provided in support of Clopidogrel Bisulphate, including SDS and any product information leaflets, has been developed and issued under the Authority of the issuing Pharmacopoeia.

Clopidogrel Bisulphate is a thienopyridine-class antiplatelet pharmaceutical agent that inhibits platelet aggregation by selectively and irreversibly binding to the P2Y12 adenosine diphosphate (ADP) receptor on platelets.
Clopidogrel Bisulphate and Clopidogrel hydrogen sulfate are the same but in different synonym supplier traded names for the same chemical compound, which is a salt form of the antiplatelet drug clopidogrel.

The name "bisulfate" is a less formal way of saying hydrogen sulfate.
CLB is Proton Pump Inhibitors (PPI).
Clopidogrel Bisulphate is a thienopyridine class of drug that inhibits platelet aggregation and thus inhibits aspects of blood clotting used to treat patients with acute coronary syndrome, myocardial infarction (MI), peripheral vascular disease and some stroke (ischemic type) patients.

Clopidogrel Bisulphate  is available in generic form.
Clopidogrel Bisulphate is an inhibitor of ADP-induced platelet aggregation acting by direct inhibition of adenosine diphosphate (ADP) binding to its receptor and of the subsequent ADP-mediated activation of the glycoprotein GPIIb/IIIa complex.

Chemically Clopidogrel Bisulphate is methyl (+)-(S)-α­(2-chlorophenyl)-6,7-dihydrothieno[3,2-c]pyridine-5(4H)-acetate sulfate (1:1).
The empirical formula of Clopidogrel Bisulphate is C16H16ClNO2S•H2SO4 and its molecular weight is 419.9.
Clopidogrel Bisulphate is a white to off-white powder.

Clopidogrel Bisulphate is practically insoluble in water at neutral pH but freely soluble at pH 1.
Clopidogrel Bisulphate also dissolves freely in methanol, dissolves sparingly in methylene chloride, and is practically insoluble in ethyl ether.

Clopidogrel Bisulphate has a specific optical rotation of about +56°.
Clopidogrel Bisulphate for oral administration is provided as either pink, round, biconvex, debossed, film-coated tablets containing 97.875 mg of Clopidogrel Bisulphate which is the molar equivalent of 75 mg of clopidogrel base or pink, oblong, debossed film-coated tablets containing 391.5 mg of Clopidogrel Bisulphate which is the molar equivalent of 300 mg of clopidogrel base.

Clopidogrel Bisulphate is the functional enantiomer of clopidogrel and a prodrug whose thiol metabolite antagonizes purine binding to the platelet purinergic receptor P2Y12 (Ki = 316 nM in human platelets).
Formulations containing Clopidogrel Bisulphate have been used in combination with aspirin to prevent vascular ischemic events in patients with acute coronary syndromes.

Clopidogrel Bisulphate is an antiplatelet drug, which belongs to the thienopyridine class of drug.
Clopidogrel Bisulphate is off-White Solid

USES and APPLICATIONS of CLOPIDOGREL BISULPHATE:
Clopidogrel Bisulphate can be used for research of heart disease and stroke.
Known by Clopidogrel hemisulfate by manufacturers, Clopidogrel Bisulphate commonly used to reduce the risk of heart disease and stroke in patients with a history of cardiovascular events.

Clopidogrel Bisulphate is used as an antithrombotic.
Clopidogrel Bisulphate is used an irreversible inhibitor of P2Y12.

Clopidogrel Bisulphate is an oral, thienopyridine class antiplatelet agent used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease.

-Veterinary Drugs and Treatments uses of Clopidogrel Bisulphate:
Clopidogrel Bisulphate, a platelet aggregation inhibitor, may be useful for preventing thrombi in susceptible cats.
Clopidogrel Bisulphate may also improve pelvic limb circulation in cats after a cardiogenic embolic event via a vasomodulating effect secondary to inhibition of serotonin release from platelets.
Research is ongoing.

USES & MECHANISM of CLOPIDOGREL BISULPHATE:
Pharmacological class: Thienopyridine; irreversible platelet P2Y₁₂ receptor antagonist
Clopidogrel Bisulphate is used prevention of arterial thromboembolism
Clopidogrel Bisulphate is used secondary prevention in myocardial infarction, stroke, peripheral arterial disease

Clopidogrel Bisulphate is often used with aspirin or for patients intolerant to aspirin
Clopidogrel Bisulphate is recommended in clinical guidelines for acute coronary syndromes and stenting

CLINICAL PHARMACOLOGY of CLOPIDOGREL BISULPHATE:
Mechanism of Action and Pharmacodynamic Properties
Clopidogrel Bisulphate is a prodrug, one of whose metabolites is an inhibitor of platelet aggregation.

A variety of drugs that inhibit platelet function have been shown to decrease morbid events in people with established cardiovascular atherosclerotic disease as evidenced by stroke or transient ischemic attacks, myocardial infarction, unstable angina or the need for vascular bypass or angioplasty.
This indicates that platelets participate in the initiation and/or evolution of these events and that inhibiting platelet function can reduce the event rate.

BIOCHEM/PHYSIOL ACTIONS of CLOPIDOGREL BISULPHATE:
Clopidogrel Bisulphate is an antithrombotic antiplatelet agent.
Clopidogrel Bisulphate specifically and irreversibly inhibits the Purinoceptor P2Y12 subtype which inhibits ADP-induced platelet aggregation.
Clopidogrel Bisulphate is the active isomer.

BENEFITS & CHARACTERISTICS of CLOPIDOGREL BISULPHATE:
*Effective antiplatelet agent for reducing risks of heart attack and stroke, particularly in high-risk patients
*Long-lasting platelet inhibition (one dose covers ~5 days)
*Widely recommended in cardiovascular treatment guidelines
*Available in fixed-dose combinations (e.g., with aspirin)
*Alternative for patients intolerant to aspirin

MANUFACTURING PROCESS of CLOPIDOGREL BISULPHATE:
Levo-rotatory ammonium camphor-10-sulfonate is dissolved in a minimum of water and applied to the column of Amberlite IRN-77 resin.
Elution is carried out with water.

The eluted fractions containing the levo-rotatory camphor-10-sulfonic acid are lyophilized, melting point 198°C.
32 g (0.0994 mole) of racemic methyl-α-5-(4,5,6,7-tetrahydro-thieno(3,2-c)pyridyl)(2-chlorophenyl)-acetate are dissolved in 150 ml of acetone.
9.95 g (0.0397 mole) of levo-rotatory camphor-10-sulfonic acid monohydrate are added.

The clear solution is left to stand at room temperature.
After 48 hours the reaction mixture is concentrated to 50 ml and left to stand at room temperature for 24 hours.

The obtained camphor-10-sulfonic acid salt of methyl-α-5-(4,5,6,7-tetrahydro-thieno(3,2-c)pyridyl)(2-chlorophenyl)-acetate (SR 25990) are filtered off, washed with acetone and dried (yield: 55% on the basis of the starting racemate), melting point 165°C, [α]D20=+24.67 (c=1.58 g/100 ml; methanol).

The crystals obtained above are redissolved in the minimum of boiling acetone (50 ml).
The crystals obtained after cooling are filtered off, washed with acetone and dried (yield: 88%), m.p. 165°C, [α]D20=+24.75 (c=1.68 g/100 ml; methanol).

12 g (0.022 mole) of the pure camphor-10-sulfonic acid salt of methyl-α-5-(4,5,6,7-tetrahydro-thieno(3,2-c)pyridyl)(2-chlorophenyl)-acetate are dissolved in a minimum of water.
After cooling to 5°C, the aqueous solution obtained is made alkaline with a saturated aqueous solution of sodium hydrogen carbonate.

The alkaline aqueous phase is extracted with dichloromethane.
The organic extracts are dried over anhydrous sodium sulfate.

On evaporation of the solvent a colorless oil of dextro-rotatory methyl-α-5-(4,5,6,7-tetrahydro-thieno(3,2-c)pyridyl)(2-chlorophenyl)-acetate is obtained (quantitative yield).

Oil, [α]D20=+51.52 (c=1.61 g/100 ml; methanol).
800 ml of a saturated aqueous solution of sodium bicarbonate are added to a suspension of 200 g of SR 25990 in 800 ml of dichloromethane.

After vigorous shaking, the organic phase is separated, dried over sodium sulfate and the solvent is removed under reduced pressure.
The residue is dissolved in 500 ml of ice-cold acetone and 20.7 ml of concentrated sulfuric acid (93.64%) are added drop-wise.

The precipitate formed is isolated by filtration and washed with 1 L of acetone, then dried in a vacuum oven at 50°C.
139 g of pure white crystals of hydrogen sulfate of dextro-rotatory methyl-α-5-(4,5,6,7-tetrahydro-thieno(3,2-c)pyridyl)(2-chlorophenyl)-acetate (SR 25990 C) are thus obtained, m.p. 184°C, [α]D20=+55.10 (c=1.891 g/100 ml; methanol).

PHARMACOKINETICS & PHARMACODYNAMICS of CLOPIDOGREL BISULPHATE:
Prodrug metabolized in liver (via CYP2C19) into an active thiol metabolite
Onset: ~2 hours
Duration: ~5 days (due to irreversible binding to platelets)
Bioavailability: >50%, protein bound ~94–98%
Elimination half‑life (inactive metabolite): 7–8 hours; excreted ~50% kidney, 46% bile

PHYSICAL and CHEMICAL PROPERTIES of CLOPIDOGREL BISULPHATE:
IUPAC Name: (S)-methyl 2-(2‑chlorophenyl)-2-(6,7‑dihydro‑4H‑thieno[3,2‑c]pyridin‑5‑yl)acetate hydrogen sulfate 
CAS Number: 120202‑66‑6 
EC (European Community) Number: 686‑767‑8 
PubChem CID: 115366 (for bisulfate salt)
Molecular Formula: C₁₆H₁₆ClNO₂S·H₂SO₄
Molecular Weight: ~419.9 g/mol 
Appearance: Off‑white to white solid 
Melting point: ~174–176 °C (some sources report 184 °C) 
Solubility:
Very poorly soluble in neutral water (~50 mg/L)
Soluble in acidic aqueous solutions (pH~1), methanol, DMSO (~26 mg/mL) 

Optical Activity: [α]D +54 to +70° (methanol, c = 0.5)
CAS Number: 120202-66-6
EC Number: 686-767-8 (or 601-679-1)
Molecular Formula: C₁₆H₁₆ClNO₂S·H₂SO₄
Molecular Weight: ~419.9 g/mol
Appearance: White/off-white solid
Melting Point: ~174–176 °C
Solubility: Very low in neutral water; soluble in acidic media, methanol, DMSO (~26 mg/mL)
Form: Solid
Color: White

Mechanism: Prodrug that irreversibly inhibits P2Y₁₂ receptor
Uses: Prevents arterial thrombosis in myocardial infarction, stroke, stents, peripheral vascular disease
Pharmacokinetics: Onset ~2 hours; duration ~5 days; metabolized by CYP2C19
Hazards: Corrosive; environmental toxicity; respiratory, skin, eye damage
Storage: 2–8 °C, ventilated, tightly sealed
CBNumber: CB1341210
MDL Number: MFCD00876395
MOL File: 120202-66-6.mol
BRN: 9967887

BCS Class: 2
InChI: InChI=1/C16H16ClNO2S.H2O4S/c1-20-16(19)15(12-4-2-3-5-13(12)17)18-8-6-14-11(10-18)7-9-21-14;1-5(2,3)4/h2-5,7,9,15H,6,8,10H2,1H3;(H2,1,2,3,4)/t15-;/s3
InChIKey: FDEODCTUSIWGLK-RSAXXLAASA-N
SMILES: S(O)(O)(=O)=O.C@@H(N1CCC2SC=CC=2C1)C(=O)OC |&1:5,r|
FDA UNII: 08I79HTP27
NCI Drug Dictionary: Clopidogrel bisulfate
UNSPSC Code: 41116107

NACRES: NA.24
PubChem Substance ID: 329822595
Beilstein Number: 9967887
Physical State: Solid
Color: No data available
Odor: No data available
Melting point/freezing point: Melting point: 184 °C
Initial boiling point and boiling range: No data available
Flammability (solid, gas): No data available

Upper/lower flammability or explosive limits: No data available
Flash point: No data available
Autoignition temperature: No data available
Decomposition temperature: No data available
pH: No data available
Viscosity:
Viscosity, kinematic: No data available
Viscosity, dynamic: No data available
Water solubility: No data available

Partition coefficient: n-octanol/water: No data available
Vapor pressure: No data available
Density: No data available
Relative density: No data available
Relative vapor density: No data available
Particle characteristics: No data available
Explosive properties: Not classified as explosive.
Oxidizing properties: None
Other safety information: No data available

CAS number: 120202-66-6
Empirical Formula: C16H16ClNO2S·H2SO4
Molecular weight: 419.9 g/mol
PubChem Substance ID: 24892408
Storage temperature: 2–8 °C
Physical appearance: White powder
Purity (HPLC area % normalized): ≥98%
Boiling Point: 423.7 °C at 760 mmHg

Melting Point: 184 °C
Molecular Formula: C16H18ClNO6S2
Molecular Weight: 419.900 g/mol
Flash Point: 210 °C
Exact Mass: 419.026398
PSA: 140.76000
LogP: 4.03980
Vapour Pressure: 8.71E-09 mmHg at 25 °C
Storage condition: 2–8 °C

FIRST AID MEASURES of CLOPIDOGREL BISULPHATE:
-Description of first-aid measures
*General advice:
Show this material safety data sheet to the doctor in attendance.
*If inhaled:
After inhalation: 
Fresh air.
*In case of skin contact: 
Take off immediately all contaminated clothing. 
Rinse skin with
water/ shower.
*In case of eye contact:
After eye contact: 
Rinse out with plenty of water. 
Call in ophthalmologist. 
Remove contact lenses.
*If swallowed:
After swallowing: 
Immediately make victim drink water (two glasses at most). 
Consult a physician.
-Indication of any immediate medical attention and special treatment needed.
No data available

ACCIDENTAL RELEASE MEASURES of CLOPIDOGREL BISULPHATE:
-Environmental precautions:
Do not let product enter drains.
-Methods and materials for containment and cleaning up:
Cover drains. 
Collect, bind, and pump off spills. 
Observe possible material restrictions. 
Take up dry. 
Dispose of properly. 
Clean up affected area.

FIRE FIGHTING MEASURES of CLOPIDOGREL BISULPHATE:
-Extinguishing media:
*Suitable extinguishing media:
Carbon dioxide (CO2) 
Foam 
Dry powder
*Unsuitable extinguishing media:
For this substance/mixture no limitations of extinguishing agents are given.
-Further information:
Prevent fire extinguishing water from contaminating surface water or the ground water system.

EXPOSURE CONTROLS/PERSONAL PROTECTION of CLOPIDOGREL BISULPHATE:
-Control parameters:
--Ingredients with workplace control parameters:
-Exposure controls:
--Personal protective equipment:
*Eye/face protection:
Use equipment for eye protection. 
Safety glasses
*Body Protection:
protective clothing
*Respiratory protection:
Recommended Filter type: Filter A 
-Control of environmental exposure:
Do not let product enter drains.

HANDLING and STORAGE of CLOPIDOGREL BISULPHATE:
-Conditions for safe storage, including any incompatibilities:
*Storage conditions:
Tightly closed. 
Dry.

STABILITY and REACTIVITY of CLOPIDOGREL BISULPHATE:
-Chemical stability:
The product is chemically stable under standard ambient conditions (room temperature).
-Possibility of hazardous reactions:
No data available