Ondansetron Hydrochloride Dihydrate CAS 103639-04-9 Assay 98.0~102.0%

Short Description:

Chemical Name: Ondansetron Hydrochloride Dihydrate

CAS: 103639-04-9

Assay: 98.0~102.0% (Calculated on the anhydrous basis)

Appearance: White or Off-White Crystalline Powder

A Specific Serotonin (5-HT3) Receptor Antagonist. Antiemetic

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Description:

Shanghai Ruifu Chemical is the leading manufacturer of Ondansetron Hydrochloride Dihydrate (CAS: 103639-04-9) with high quality. Ruifu can provide worldwide delivery, competitive price, excellent service, small and bulk quantities available. Purchase Ondansetron Hydrochloride Dihydrate, Please contact: alvin@ruifuchem.com

Related Intermediates:

Related Intermediates of Ondansetron Hydrochloride Dihydrate

1,3-Cyclohexanedione	CAS 504-02-9
1,2,3,9-Tetrahydro-9-Methyl-4H-Carbazole-4-one	CAS 27387-31-1
Ondansetron Hydrochloride Dihydrate	CAS 103639-04-9

Chemical Properties:

Chemical Name	Ondansetron Hydrochloride Dihydrate
Synonyms	Ondansetron HCl Dihydrate; 1,2,3,9-Tetrahydro-9-Methyl-3-[(2-Methyl-1H-imidazol-1-yl)methyl]-4H-Carbazol-4-one Hydrochloride Dihydrate; Emeset; GR 38032 Hydrochloride Dihydrate; SN 307 Hydrochloride Dihydrate; GR 3832 HCl 2H2O; SN-37 HCl 2H2O; NSC665799 HCl 2H2O
Stock Status	In Stock, Commercial Scale
CAS Number	103639-04-9 (Dihydrate)
Related CAS RN	99614-02-5 (Base) & 99614-01-4 (Anhydrous)
Molecular Formula	C18H19N3O·HCl·2H2O
Molecular Weight	365.86 g/mol
Melting Point	176.0 to 180.0℃
Sensitive	Heat Sensitive
Water Solubility	Soluble in Water (>5 mg/ml)
Storage Temp.	Cool & Dry Place (2~8℃)
COA & MSDS	Available
Brand	Ruifu Chemical

Specifications:

Items	Inspection Standards	Results
Appearance	White to Off-White Crystalline Powder	Complies
Identification
1. UV	Max 209, 248, 267, 310nm	Qualified
2. IR spectrum	Conforms to Structure	Qualified
3. Discrimination of the Chloride	Forward Reaction	Qualified
Water by Karl Fischer	9.0~10.5%	9.7%
Residue on Ignition	≤0.10%	0.03%
Heavy Metals (Pb)	≤10ppm	<10ppm
Ondansetron Related Compound C	≤0.20%	0.09%
Ondansetron Related compound D	≤0.10%	0.04%
Imidazole	≤0.20%	0.02%
2-Methylimidazole	≤0.20%	0.02%
Ondansetron Related Compound A	≤0.20%	0.05%
Other Unknown Single Impurity	≤0.10%	0.07%
Total Impurities	≤0.50%	0.29%
Residual Solvent
Ethanol	≤5000ppm	240ppm
Assay	98.0~102.0% (Calculated on the anhydrous basis)	99.81%
Conclusion	The product has been tested & complies with the specifications

Package/Storage/Shipping:

Package: Bottle, Aluminium foil bag, 25kg/Cardboard Drum, or according to customer's requirement.
Storage Condition: Store in a tightly closed container. Store in a cool, dry (2~8℃) and well-ventilated warehouse away from incompatible substances. Protect from light and moisture.
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Technical Support: Technology solution available

Custom Synthesis Service: Ranged from grams to kilos

High Quality: Established a complete quality assurance system

FAQ:

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Advantages? Superior quality, affordable price, professional services and technical support, fast delivery.

Quality Assurance? Strict quality control system. Professional equipment for analysis include NMR, LC-MS, GC, HPLC, ICP-MS, UV, IR, OR, K.F, ROI, LOD, MP, Clarity, Solubility, Microbial limit test, etc.

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103639-04-9 - Risk and Safety:

Risk Codes
R25 - Toxic if swallowed
R36/37/38 - Irritating to eyes, respiratory system and skin.
Safety Description
S45 - In case of accident or if you feel unwell, seek medical advice immediately (show the label whenever possible.)
S37/39 - Wear suitable gloves and eye/face protection
S26 - In case of contact with eyes, rinse immediately with plenty of water and seek medical advice.
UN IDs UN 2811 6.1/PG 3
WGK Germany 3
RTECS FE6375500
HS Code 29339900
Hazard Class 6.1(a)
Packing Group II

103639-04-9 - Application:

Ondansetron Hydrochloride Dihydrate (CAS: 103639-04-9) is a specific serotonin (5-HT3) receptor antagonist. Antiemetic. Ondansetron Hydrochloride Dihydrate is used to prevent nausea and vomiting that may be caused by surgery, cancer chemotherapy, or radiation treatment. The 5-HT3 receptor antagonists in Ondansetron are the primary drugs used to treat and prevent chemotherapy-induced nausea and vomiting and radiotherapy-induced nausea and vomiting, through blocking the actions of chemicals in the body. The efficacy is better than metoclopramide while less sedating than cyclizine or droperidol. However, it has little effect on vomiting caused by motion sickness. It can be given by mouth, by injection into a muscle or into a vein.

Ondansetron and Granisetron, Dolasetron are three common clinically used antiemetics, ondansetron is an effective serotonin (5-HT3) receptor blocker which is reversible and selective, for α1, α2, β1, β2-adrenergic receptors and the histamine H1, H2 receptors ,it has the minimal effect ,for H receptors, central and peripheral dopaminergic receptors ,it has no antagonistic effect ,it can suppress the chemotherapy and radiotherapy-induced nausea and vomiting. Compared with metoclopramide, its antiemetic effect is stronger and it has no extrapyramidal reactions. For vomiting induced by cisplatin, cyclophosphamide, doxorubicin, etc. it can produce rapid and strong antiemetic effect. It is suitable not only for the treatment of nausea and vomiting caused by the cytotoxic chemotherapy and radiation therapy, but also for the prevention and treatment of nausea and vomiting induced by surgeries. Ondansetron works as a transit point between the visceral afferent nerve activated in the gastrointestinal tract and vomiting center within the spinal cord , which leads to the diaphragm and abdominal muscles movements. Chemotherapy and radiation therapy can cause intestinal 5-HT release and cause vagus nerve stimulation by 5-HT3 receptor ,which causes vomiting reflex. This product blocks this reflex occurring ,at the same time it blocks the vomiting triggered by the central action. The mechanism about postoperative nausea and vomiting is unknown. Ondansetron in combination with dexamethasonecan can enhance the anti-emetic effect.

103639-04-9 - Side Effects:

This causes vagal afferent discharge, inducing vomiting. In binding to 5-HT3 receptors, ondansetron blocks serotonin stimulation, hence vomiting, after emetogenic stimuli such as cisplatin. Headache is the most frequently reported adverse effect of these medications.

103639-04-9 - Safety Profile:

A poison by intravenous route.Human systemic effects by intravenous route: jaundice. When heated to decomposition it emits toxic vapors ofNOx.

103639-04-9 - Veterinary Drugs and Treatments:

Used as an antiemetic when conventional antiemetics are ineffective, such as when administering cisplatin or for other causes of intractable vomiting. The use of ondansetron in cats is somewhat controversial and some state it should not be used in this species.

Drug interactions Potentially hazardous interactions with other drugs.

103639-04-9 - USP35 Standard:

Ondansetron Hydrochloride contains not less than 98.0 percent and not more than 102.0 percent of C18H19N3O·HCl, calculated on the anhydrous basis.

Packaging and storage-Preserve in tight, light-resistant containers. Store at 25

, excursions permitted between 15

and 30

USP Reference standards <11>-

USP Ondansetron Hydrochloride RS

USP Ondansetron Related Compound A RS

3[(Dimethylamino)methyl]-1,2,3,9-tetrahydro-9-methyl-4H-carbazol-4-one.

USP Ondansetron Resolution Mixture RS

Ondansetron hydrochloride having approximately 0.4% w/w of both ondansetron related compound A and 6,6¢-methylene bis-[(1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)-methyl]-4H-carbazol-4-one)]

USP Ondansetron Related Compound C RS
1,2,3,9-Tetrahydro-9-methyl-4H-carbazol-4-one.

USP Ondansetron Related Compound D RS
1,2,3,9-Tetrahydro-9-methyl-3-methylene-4H-carbazol-4-one.

Identification-

A: Infrared Absorption <197M>.

B: Dissolve 20 mg in 2 mL of water, add 1 mL of 2 M nitric acid, and filter: the filtrate responds to the test for Chloride <191>.

Water, Method Ia <921>: between 9.0% and 10.5%.

Residue on ignition <281>: not more than 0.1%.

Limit of ondansetron related compound D-

Mobile phase- Prepare a filtered and degassed mixture of 0.02 M monobasic potassium phosphate (previously adjusted with 1 M sodium hydroxide to a pH of 5.4) and acetonitrile (80:20). Make adjustments if necessary (see System Suitability under Chromatography <621>).

Standard solution-Dissolve an accurately weighed quantity of USP Ondansetron Related Compound D RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 0.4 µg per mL.

System suitability solution-Dissolve suitable quantities of USP Ondansetron Related Compound D RS and USP Ondansetron Related Compound C RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a concentration of about 0.6 µg per mL and 1 µg per mL, respectively.

Test solution-Transfer about 50 mg of Ondansetron Hydrochloride, accurately weighed, to a 100-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix.

Chromatographic system (see Chromatography <621>)-The liquid chromatograph is equipped with a 328-nm detector and a 4.6-mm × 25-cm column that contains packing L10. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.8 for ondansetron related compound C and 1.0 for ondansetron related compound D; and the resolution, R, between ondansetron related compound C and ondansetron related compound D is not less than 1.5. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the column efficiency determined from the analyte peak is not less than 400 theoretical plates; and the relative standard deviation for replicate injections is not more than 2.0%.

Procedure- Separately inject equal volumes (about 20 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the percentage of ondansetron related compound D in the portion of Ondansetron Hydrochloride taken by the formula:

10,000(C/W)(rU / rS)

in which C is the concentration, in mg per mL, of USP Ondansetron Related Compound D RS in the Standard solution; W is the weight, in mg, of Ondansetron Hydrochloride taken to prepare the Test solution; and rU and rS are the peak areas obtained from the Test solution and the Standard solution, respectively: not more than 0.10% is found.

Chromatographic purity-

method i-

Resolution solution-Dissolve a quantity of USP Ondansetron Resolution Mixture RS in methanol, and dilute quantitatively, and stepwise if necessary, with methanol to obtain a solution having a known concentration of 12.5 mg per mL.

Standard solutions-Dissolve an accurately weighed quantity of USP Ondansetron Hydrochloride RS in methanol, and mix to obtain a solution having a known concentration of about 0.25 mg per mL. Quantitatively dilute this solution with methanol to obtain Standard solutions, designated below by letter, having the following compositions:

Standard solution	Dilution	Concentration (µg RS per mL)	Percentage (%, for comparison with test specimen)
A	(1 in 5)	50	0.4
B	(1 in 10)	25	0.2
C	(1 in 20)	12.5	0.1

Test solution-Dissolve an accurately weighed quantity of Ondansetron Hydrochloride in methanol to obtain a solution containing 12.5 mg per mL.Procedure-Separately apply 20 µL of the Test solution, 20 µL of each Standard solution, and 20 µL of the Resolution solution to a thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Develop the chromatogram in a solvent system consisting of a mixture of chloroform, ethyl acetate, methanol, and ammonium hydroxide (90:50:40:1) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the chamber, mark the solvent front, and allow the solvent to evaporate. Examine the plate under short-wavelength UV light: complete resolution of the three components of the Resolution solution spot is found. Compare the intensities of any secondary spots observed in the chromatogram of the Test solution with those of the principal spots in the chromatograms of the Standard solutions: any secondary spot from the chromatogram of the Test solution having an RF value corresponding to that of the uppermost secondary spot of the Resolution solution is not larger or more intense than the principal spot obtained from Standard solution A (0.4%); and no other secondary spot from the chromatogram of the Test solution is larger or more intense than the principal spot obtained from Standard solution B (0.2%).

method ii-

Mobile phase and Chromatographic system-Proceed as directed in the Assay.

Standard solution-Proceed as directed for Standard preparation in the Assay.

Test solution-Use the Assay preparation.

Procedure-Separately inject equal volumes (about 10 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of each impurity in the portion of Ondansetron Hydrochloride taken by the formula:

50,000(C/W)(1/F)(ri / rS)
in which C is the concentration, in mg per mL, of USP Ondansetron Hydrochloride RS in the Standard solution; W is the weight, in mg, of Ondansetron Hydrochloride taken to prepare the Test solution; F is the relative response factor of the impurities as described in the accompanying table; ri is the peak area for each impurity in the Test solution; and rS is the peak area of ondansetron obtained from the Standard solution: it meets the requirements given in the accompanying table.

Compound Name	Relative Retention Time	Relative Response Factor	Limit (%)
Ondansetron related compound C	about 0.32	1.2	0.2
Ondansetron related compound D*	about 0.34	—	0.1
Imidazole	about 0.49	0.3	0.2
2-methylimidazole	about 0.54	0.4	0.2
Ondansetron	1.0	—	—
Ondansetron related compound A	about 1.10	0.8	0.2
Unknown	—	1.0	0.1
Total	—	—	0.5
* Quantified in the test for Limit of ondansetron related compound D.

Assay-

Mobile phase-Prepare a filtered and degassed mixture of 0.02 M monobasic sodium phosphate (previously adjusted with 1 M sodium hydroxide to a pH of 5.4) and acetonitrile (50:50). Make adjustments if necessary (see System Suitability under Chromatography <621>).

Standard preparation-Dissolve an accurately weighed quantity of USP Ondansetron Hydrochloride RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 90 µg per mL.

System suitability solution-Dissolve suitable quantities of USP Ondansetron Hydrochloride RS and USP Ondansetron Related Compound A RS in Mobile phase, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution containing about 90 µg per mL and 20 µg per mL, respectively.

Assay preparation-Transfer about 45 mg of Ondansetron Hydrochloride, accurately weighed, to a 50-mL volumetric flask, dissolve in and dilute with Mobile phase to volume, and mix. Pipet 5.0 mL of this solution into a 50-mL volumetric flask, dilute with Mobile phase to volume, and mix.

Chromatographic system (see Chromatography <621>)-The liquid chromatograph is equipped with a 216-nm detector and a 4.6-mm × 25-cm column that contains packing L10. The flow rate is about 1.5 mL per minute. Chromatograph the System suitability solution, and record the peak responses as directed for Procedure: the relative retention times are about 1.0 for ondansetron and 1.1 for ondansetron related compound A; and the resolution, R, between ondansetron related compound A and ondansetron is not less than 1.5. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor is not more than 2.0; and the relative standard deviation for replicate injections is not more than 1.5%.

Procedure-Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantity, in mg, of C18H19N3O·HCl in the portion of Ondansetron Hydrochloride taken by the formula:

500C(rU / rS)
in which C is the concentration, in mg per mL, of USP Ondansetron Hydrochloride RS in the Standard preparation; and rU and rS are the peak areas obtained from the Assay preparation and the Standard preparation, respectively.

103639-04-9 - Production Method:

Method 1: After the reaction of 2-Bromoaniline and 1,3-Cyclohexanedione, the tetrahydrocarbazole derivative is formed, and the compound (III) is obtained by reacting with dimethylamine and diformaldehyde, and introducing dimethylaminomethyl at the 2-position. 3.80G of compound (III) was reacted with methyl iodide to give 5.72g of compound (IV) by quaternizing the side chain amino group while introducing the methyl group at position 9. 2.0g of compound (IV) and 2-methyl-1h-imidazole were reacted in dimethylformamide with stirring at 95℃. To obtain 0.60G of Ondansetron.

Method 2: The reaction of cyclohexanone and phenylhydrazine gave tetrahydrocarbazole in 85% yield. Dissolve it in tetrahydrofuran and water, add 2,3 Dropwise at 0 °c in nitrogen, A solution of 5, 6-tetrachloro-1,4-benzoquinone in tetrahydrofuran was stirred to give the oxidation product (II) in 67.4% yield. Compound (II), ethanol, concentrated hydrochloric acid, paraformaldehyde and dimethylamine hydrochloride were refluxed together. After the treatment, the product (V) was obtained by adding concentrated hydrochloric acid to acetone and stirring at 50℃. In 71.7% yield. Compound (V) and 2-methylimidazole were reacted in water at 110℃. To obtain compound (VI) in 70.9% yield. Compound (VI), methyl iodide and potassium carbonate were stirred at room temperature until the solid disappeared. It was poured into water, stirred, filtered, washed with water, and recrystallized from methanol to obtain ondansetron in 57.2% yield. Dissolve it in a mixture of acetone and water, By adding concentrated hydrochloric acid to the reaction, ondansetron hydrochloride dihydrate was obtained with a yield of 92.6%.

Method 3: compound (II), potassium carbonate, acetone and dimethyl sulfate were stirred at room temperature. Compound (VII) was obtained in a yield of 91%. Compound (VII) was dissolved in ethanol and a mixture of human paraformaldehyde and dimethylamine hydrochloride was added in portions under reflux. Refluxing. After treatment, compound (VIII) was obtained in 67% yield. (Viii) dissolved in anhydrous ethanol, hydrogen chloride gas, its hydrochloride. The hydrochloride was added to water and 2 was added at 50℃. Methylimidazole, refluxing ondansetron, yield 70%. It was dissolved in isopropanol, water and concentrated hydrochloric acid, and stirred at room temperature to obtain ondansetron hydrochloride dihydrate in a yield of 90.5%.