122883-93-6
2H-Indol-2-one,5-[2-[4-(1,2-benzisothiazol-3-yl)-1-piperazinyl]ethyl]-6-chloro-1,3-dihydro-,hydrochloride (1:1)
CAS: 122883-93-6
Molecular Formula: C21H21ClN4OS
122883-93-6 - Names and Identifiers
122883-93-6 - Physico-chemical Properties
| Molecular Formula | C21H21ClN4OS |
| Molar Mass | 412.943 |
| Melting Point | >300 °C |
| Boling Point | 554.8 °C at 760 mmHg |
| Flash Point | 289.3 °C |
| In vitro study | Ziprasidone has high affinity for human 5-HT receptors and human dopamine D(2) receptors. Ziprasidone is a 5-HT(1A) receptor agonist and a 5-HT(2A),5-HT(2C), and 5-HT(1B/1D) receptor antagonist. Ziprasidone inhibits neuronal uptake of 5-HT and norepinephrine, with an effect comparable to that of the antidepressant imipramine. In stably transfected HEK-293 cells, Ziprasidone blocked the wild-type hERG current in a voltage-and concentration-dependent manner with IC(50) at 120nm. Ziprasidone exhibited minimal tonic blockade of hERG currents, as estimated during depolarizing voltages (-20 or 30mV), or as assessed by the envelope of a tail suspension experiment (30mV). Ziprasidone significantly increased the time constant of slow response to hERG current deactivation (-50mV). |
| In vivo study | Ziprasidone showed a low blocking effect on wild-type hERG currents, with an IC(50) of 2.8 mM in Xenopus oocytes. In rats, Ziprasidone inhibited the significant increase in food intake produced by olanzapine, suggesting an inherent protective mechanism against the drug-induced increase in food intake. Ziprasidone causes a significant increase in NGF and ChAT immunoreactivity in the dentate gyrus (DG),CA1, and CA3 regions of the rat hippocampus. In anesthetized rats, such as the atypical antipsychotic clozapine (ED50=250 mg/kg I. v.) and olanzapine (ED50=1000 mg/kg I. v.), ziprasidone was also able to dose-dependently slow the activity of the midseam unit (ED50=300 mg/kg I. v.). |
122883-93-6 - Standard
Authoritative Data Verified Data
This product is 5-[2-[4-(l, 2-benzisothiazol-3-yl)-l-piperazinyl] ethyl] -6-chloro-1, 3-dihydro-2h-indol-2-one hydrochloride hemihydrate. C21H21C1N40S • HCl should be 98.0% to 102.0% based on water and solvent-free material.
Last Update：2024-01-02 23:10:35
122883-93-6 - Trait
Authoritative Data Verified Data
- This product is white to light orange-red crystalline powder; Hygroscopicity; Odorless.
- This product is slightly soluble in N,N-dimethylformamide or methanol, and insoluble in dichloromethane, anhydrous ethanol or water.
Last Update：2022-01-01 15:04:00
122883-93-6 - Differential diagnosis
Authoritative Data Verified Data
- in the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
- The infrared absorption spectrum of this product should be consistent with that of the reference product (General rule 0402).
- this product of ethanol solution chloride identification (1) of the reaction (General 0301).
Last Update：2022-01-01 15:04:00
122883-93-6 - Exam
Authoritative Data Verified Data
Related substances I
take an appropriate amount of this product, add methanol-water-hydrochloric acid (20:5:0.01) to dissolve and dilute to make a solution containing about 0.5mg per 1 ml as a test solution; an appropriate amount was taken in a precise amount and quantitatively diluted with the above solvent to prepare a solution containing about 2.5ug per 1 ml as a control solution. According to the chromatographic conditions under the content determination item, 20ul of the test solution and the control solution are respectively injected into the liquid chromatograph, and the chromatogram is recorded to 1.5 times of the retention time of the main component peak. If there is an impurity peak before the ziprasidone peak in the chromatogram of the test solution, the area of a single impurity peak shall not be greater than the area of the main peak of the control solution (0.5%).
Related substances II
The Test Solution and the control solution under item I of related substances are taken as the test solution and the control solution respectively, and the test is carried out according to high performance liquid chromatography (General rule 0512), using octanosilane bonded silica gel as filler; Phosphate buffer solution (take potassium dihydrogen phosphate 6.8g, add water 900ml to dissolve, adjust the pH value to 6.0 with 5mol/L sodium hydroxide solution, add water to 1000ml)-Acetonitrile-methanol (8:11:1) as mobile phase, the detection wavelength was 229nm. 20 u1 of the test solution and the control solution were respectively injected into the human liquid chromatograph, and the chromatogram was recorded to 4 times of the retention time of the main component peak. If there is an impurity peak after the ziprasidone peak in the chromatogram of the test solution, the area of a single impurity peak shall not be greater than the area of the main peak of the control solution (0.5%).
The total amount of impurities under related substances I and related substances II shall not exceed 1.5%.
residual solvent
take this product 0.25g, precision weighing, precision plus dimethyl sulfoxide 5ml dissolved as a test solution; Another precision weighing methanol, ethanol, N-hexane, N,N-dimethylformamide, the appropriate amount of dichloromethane, toluene and tetrahydrofuran is added and diluted quantitatively with dimethyl sulfoxide to prepare a mixed solution containing about 150ug, 250ug, 14.5ug, 44ug, 30ug, 44.5ug and 36ug per lml, respectively, as a control solution. According to the test for determination of residual solvents (General 0861 third method), the capillary column with polyethylene glycol (PEG-20M) (or similar polarity) as stationary liquid is used as the chromatographic column; The initial temperature is 40°C, and the maintenance time is 20 minutes, the temperature was then increased to 220°C at a rate of 10°C per minute for 4 minutes; The detector temperature was 250°C; And the inlet temperature was 180°C. The lul of the test solution and the reference solution were accurately measured and injected into the human gas chromatograph respectively, and the chromatogram was recorded. Based on the peak area calculated by external standard method, the residues of methanol, ethanol, N-hexane, N,N-dimethylformamide, dichloromethane, toluene and tetrahydrofuran shall meet the requirements.
moisture
take this product, according to the determination of moisture (General rule 0832 first method 1), the water content should not exceed 3.0%.
ignition residue
take l.Og of this product and check it according to law (General rule 0841). The residue left shall not exceed 0.1%.
Heavy metals
The residue left under the item of taking the ignition residue shall not contain more than 20 parts per million of heavy metal when examined by law (General rule 0821, Law II).
Last Update：2022-01-01 15:04:01
122883-93-6 - Content determination
Authoritative Data Verified Data
measured by high performance liquid chromatography (General 0512).
chromatographic conditions and system suitability test
octyl silane bonded silica gel as filler; Phosphate buffer (take potassium dihydrogen phosphate 6.8g, add water 900ml to dissolve, adjust pH to 3.0 with phosphoric acid, add water to 1000ml)-Methanol (3:2) as mobile phase; Detection wavelength at 229nm. The theoretical plate number is not less than 2000 based on the ziprasidone peak.
assay
take about 23mg of this product, weigh it accurately, put it in a 50ml measuring flask, add an appropriate amount of 60% methanol solution, shake to dissolve it, dilute it to the scale, and shake it well, as a sample solution, 20ul was accurately measured, injected into the liquid chromatograph, and the chromatogram was recorded. Another ziprasidone hydrochloride reference substance was taken and determined by the same method. According to the external standard method to calculate the peak area, that is.
Last Update：2022-01-01 15:04:02
122883-93-6 - Category
Authoritative Data Verified Data
antipsychotics.
Last Update：2022-01-01 15:04:02
122883-93-6 - Storage
Authoritative Data Verified Data
sealed and stored in a dry place.
Last Update：2022-01-01 15:04:02
122883-93-6 - Ziprasidone hydrochloride tablets
Authoritative Data Verified Data
This product contains ziprasidone hydrochloride (c21h21c11n40s • HCl) should be 90.0% to 110.0% of the label.
trait
This product is a white-like to light red tablet or film-coated tablet, and the film-coated tablet is white-like to light red after removal of the coating.
identification
- take an appropriate amount of fine powder (about 10mg of ziprasidone hydrochloride) of this product (film-coated tablets are not coated) and put it in a 50ml measuring flask, add the dissolution medium under the item of dissolution to dissolve and dilute to the scale, shake well, filter, Take 5ml of the continued filtrate, dilute to 25ml with the above solvent, shake well, there is an absorption maximum at a wavelength of 316mn as determined by UV-Vis spectrophotometry (General rule 0401).
- in the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
- take an appropriate amount of the fine powder of this product, and shake with ethanol to dissolve ziprasidone hydrochloride, filter, and the filtrate shows chloride to identify the reaction of (1) (General rule 0301).
examination
- Related substances I take an appropriate amount of the fine powder of this product, add methanol-water-hydrochloric acid (20:5:0.01) to dissolve and dilute to prepare a solution containing about 0.5mg of ziprasidone hydrochloride per 1 ml, the filtrate was filtered, and the filtrate was taken as a test solution; An appropriate amount was taken in a precise amount, and the above solvent was added for quantitative dilution to prepare a solution containing about 2.5ug of ziprasidone hydrochloride per 1 ml as a control solution. Determination of related substances of ziprasidone hydrochloride according to item I. If there is an impurity peak before the ziprasidone peak in the chromatogram of the test solution, the area of a single impurity peak shall not be more than 2 times (1.0%) the area of the main peak of the control solution.
- Related substances II the test solution and the control solution under item I of related substances are taken as the test solution and the control solution, determination of related substances of ziprasidone hydrochloride according to n item method. If there is an impurity peak after the ziprasidone peak in the chromatogram of the test solution, the area of a single impurity peak shall not be more than 2 times (1.0%) of the area of the main peak of the control solution.
- the total amount of impurities under related substances I and related substances II shall not exceed 2.0%.
- Content uniformity take 1 tablet of this product, put it in a 50ml measuring flask, add an appropriate amount of 60% methanol solution, sonicate (about 15 minutes) to dissolve ziprasidone hydrochloride, and let it cool, dilute with 60% methanol solution to the scale, shake, filter, take the filtrate as the test solution, and determine the content according to the method under the content determination item, which should comply with the regulations (General 0941).
- dissolution of this product, according to the dissolution and release determination method (General 0931 second method), with acetic acid-sodium acetate buffer (sodium acetate 4.0g, add glacial acetic acid, add water to dissolve and dilute to 1000ml,pH 3.6)500ml as the dissolution medium, the rotation speed is 50 rpm, operate according to law, after 45 minutes, take the appropriate amount of solution, filter, take the filtrate according to UV-visible spectrophotometry (General rule 0401), measure absorbance at the wavelength of 316nm; Take the appropriate amount of the reference solution under the content determination item, the solution containing about 40ug per 1 ml was prepared by quantitative dilution with dissolution medium, and the dissolution amount of each tablet was calculated by the same method. The limit is 75% of the labeled amount and shall be in accordance with the provisions.
- others shall be in accordance with the relevant provisions under the item of tablets (General rule 0101).
Content determination
- measured by high performance liquid chromatography (General 0512).
- chromatographic conditions and system suitability test using octyl silane bonded silica gel as filler; Phosphate buffer solution (6.8g of potassium dihydrogen phosphate, add water 3.0 to dissolve, adjust pH to with phosphoric acid, water was added to 1000ml)-methanol (3:2) as mobile phase; The detection wavelength was 229nm. The theoretical plate number is not less than 2000 based on the ziprasidone peak.
- determination Method: Take 20 tablets of this product (film-coated tablets are removed from coating), precisely weigh them, grind them finely, and precisely weigh an appropriate amount (equivalent to 20mg of ziprasidone hydrochloride), place them in a 50ml measuring flask, add an appropriate amount of 60% methanol solution, sonicate to dissolve ziprasidone hydrochloride, dilute to the scale with 60% methanol solution, shake, filter, and take the continued filtrate as the test solution, 20ul was accurately measured and injected into human liquid chromatograph, and the chromatogram was recorded. The reference product of ziprasidone hydrochloride, about 20mg, was accurately weighed and placed in a 50ml measuring flask, add 60% methanol solution to dissolve and dilute to the scale, shake, the same method. According to the external standard method to calculate the peak area, that is.
category
with ziprasidone hydrochloride.
specification
20mg
storage
sealed storage.
Last Update：2022-01-01 15:04:03
122883-93-6 - Ziprasidone hydrochloride capsules
Authoritative Data Verified Data
This product contains ziprasidone hydrochloride to ziprasidone (c21h21c11n40s), should be the label amount of 90.0% to 110.0%.
trait
The contents of this product are white to reddish particles or powder.
identification
- in the chromatogram recorded under the content determination item, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the reference solution.
- take an appropriate amount of the contents of this product, and shake with ethanol to dissolve ziprasidone hydrochloride, filter, and the filtrate shows chloride to identify the reaction of (1) (General rule 0301).
examination
- Related substances I take an appropriate amount of the contents of this product, add methanol-water-hydrochloric acid (20:5:0.01) to dissolve and dilute to prepare a solution containing 0.5mg of ziprasidone hydrochloride per 1 ml, the filtrate was filtered and taken as a test solution; An appropriate amount was taken in a precise amount and quantitatively diluted with the above solvent to a solution containing about 2.5ug of ziprasidone hydrochloride per 1 ml as a control solution. Determination of related substances of ziprasidone hydrochloride according to item I. If there is an impurity peak before the ziprasidone peak in the chromatogram of the test solution, the area of a single impurity peak shall not be more than 2 times (1.0%) the area of the main peak of the control solution.
- related substance I the test solution and the control solution under the related substance I were taken as the test solution and the control solution, respectively. Determination of related substances of ziprasidone hydrochloride according to n item method. If there is an impurity peak after the ziprasidone peak in the chromatogram of the test solution, the area of a single impurity peak shall not be more than 2 times (1.0%) of the area of the main peak of the control solution.
- the total amount of impurities under related substances I and related substances II shall not exceed 2.0%.
- Content uniformity (20mg specification) take 1 capsule of this product, pour the content into a 200ml measuring flask, wash the capsule shell with 60% methanol solution, and incorporate the washing solution into the measuring flask, the ziprasidone hydrochloride was dissolved by ultrasound, allowed to cool, diluted to the scale with 60% methanol solution, shaken, filtered, and the filtrate was taken as the test solution. Determination according to the method under the content determination item, should comply with the provisions (General 0941).
- dissolution of this product, according to the dissolution and release determination method (General 0931 second method), with phosphate buffer [take sodium dodecyl sulfate 20g, add 0.05mol/L sodium dihydrogen phosphate solution 1000ml (with 6mol/L sodium hydroxide solution to adjust the pH value to 7.5) to dissolve, that is, 900ml as the dissolution medium, the rotation speed is 75 revolutions per minute, operate according to law, after 45 minutes, the appropriate amount of the solution was filtered, and the filtrate was taken as the test solution. The appropriate amount of ziprasidone hydrochloride was accurately weighed, and the appropriate amount of methanol was added for ultrasonic dissolution, A solution containing approximately 24ug(20mg specification) or 48UG (40mg specification) or 72UG (60mg specification) of ziprasidone hydrochloride per 1 ml was prepared by quantitative dilution with a dissolution medium as a control solution. Determined by high performance liquid chromatography (General 0512). Octyl silane bonded to silicon as filler; 0.05mol/L potassium dihydrogen phosphate solution (The pH value was adjusted to 6.5 with 5mol/L potassium hydroxide solution)-acetonitrile (55:45) as mobile phase; The column temperature was 40 ° C.; The detection wavelength was 315nm. The theoretical plate number is not less than 2000 based on the ziprasidone peak. The LOLs of the test solution and the reference solution were respectively injected with human liquid chromatograph, and the chromatogram was recorded. The dissolution amount of each particle was calculated by the peak area according to the external standard method, and the result was multiplied by 0.9189. The limit is 75% of the labeled amount and shall be in accordance with the provisions.
- others should comply with the relevant provisions under the capsule (General 0103).
Content determination
- measured by high performance liquid chromatography (General 0512).
- chromatographic conditions and system suitability test using octyl silane bonded silica gel as filler; Phosphate buffer solution (6.8g of potassium dihydrogen phosphate, add water 3.0 to dissolve, adjust pH to with phosphoric acid, water was added to 1000ml)-methanol (60:40) as mobile phase; The detection wavelength was 229nm. The theoretical plate number is not less than 2000 based on the ziprasidone peak.
- determine the contents under the item of difference in loading amount, mix evenly, weigh an appropriate amount (about 20mg equivalent to ziprasidone) accurately, put it in a 200ml measuring flask, and add an appropriate amount of 60% methanol solution, ultrasonic dissolution of ziprasidone hydrochloride, dilute to the scale with 60% methanol solution, shake well, filter, take the continued filtrate as the test solution, and inject 20u1 into human liquid chromatograph with precision, record the chromatogram; Take an appropriate amount of ziprasidone hydrochloride reference substance, weigh it accurately, add 60% methanol solution to dissolve and quantitatively dilute to make it contain about 0 ziprasidone per 1 ml. lmg solution, the same method for determination. According to the external standard method to calculate the peak area, the result is multiplied by 0.9189.
category
with ziprasidone hydrochloride.
specification
Based on c21h21c11n40s (l)20mg (2)40mg(3)60Mg
storage
sealed storage.
Last Update：2022-01-01 15:04:04
