Irbesartan Alkylation

Irbesartan Alkylation - Names and Identifiers

Name	4'-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]biphenyl-2-carbonitrile
Synonyms	Irbint-A04 4'-[(2-Butyl-4-oxo-1 Irbesartan Alkylation Irbesartan Impurity 12 He sand hydrocarbon compound 3-diazaspiro[4.4]non-1-en-3-yl)methyl]-(1 4'-[(2-Butyl-4-oxo-1,3-diazaspiro[4,4]non-1-en-3-yl)methyl]biphenyl-2-carbonitrile 4'-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]biphenyl-2-carbonitrile [1,1'-BIPHENYL]-2-CARBONITRILE-4-[(2-BUTYL-4-OXO-1,3-DIAZASPIRO[4.4]NON-1-EN-3-YL)METHYL] 4'-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-[1,1'-biphenyl]-2-carbonitrile 4'-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]-(1,1'-biphenyl)-2-carbonitrile [1,1'-Biphenyl]-2-Carbonitrile-4-[(2-Butyl-4-Oxo-1,3-Diazaspiro[4.4]Non-1-en-3-yl) Methyl] 4'-[(2-Butyl-4-oxo-1,3-diazaspiro[4.4]non-1-en-3-yl)methyl]biphen biphenyl-2-carbonitrile [1,1'-BIPHENYL]-2-CARBONITRILE, 4'-[(2-BUTYL-4-OXO-1,3-DIAZASPIRO[4.4]NON-1-EN-3-YL)METHYL]-
CAS	138401-24-8
EINECS	423-500-4
InChI	InChI=1/C25H27N3O/c1-2-3-10-23-27-25(15-6-7-16-25)24(29)28(23)18-19-11-13-20(14-12-19)22-9-5-4-8-21(22)17-26/h4-5,8-9,11-14H,2-3,6-7,10,15-16,18H2,1H3

Irbesartan Alkylation - Physico-chemical Properties

Molecular Formula	C25H27N3O
Molar Mass	385.5
Density	1.15
Melting Point	95-97°C
Boling Point	576.5±60.0 °C(Predicted)
Flash Point	302.479°C
Solubility	soluble in Methanol
Vapor Presure	0Pa at 20℃
Appearance	Crystalline
Color	White to Almost white
pKa	2.45±0.20(Predicted)
Storage Condition	Sealed in dry,Room Temperature
Refractive Index	1.621
Physical and Chemical Properties	Density 1.15

Irbesartan Alkylation - Risk and Safety

Hazard Symbols	N - Dangerous for the environment
Risk Codes	50/53 - Very toxic to aquatic organisms, may cause long-term adverse effects in the aquatic environment.
Safety Description	S60 - This material and its container must be disposed of as hazardous waste. S61 - Avoid release to the environment. Refer to special instructions / safety data sheets.
UN IDs	3077

Irbesartan Alkylation - Standard

Authoritative Data Verified Data

This product is 2-butyl -3-[4-[2-1h-tetrazolid-5-yl) phenyl] benzyl] -1, 3-diazaspiro [4,4] non-1-en-4-one. Calculated as dried product, the content of C25H28N60 shall not be less than 99.0%.

Last Update：2024-01-02 23:10:35

Irbesartan Alkylation - Trait

Authoritative Data Verified Data

This product is white or off-white powder or crystalline powder.
This product is slightly soluble in methanol or ethanol and insoluble in water.

Last Update：2022-01-01 11:32:08

Irbesartan Alkylation - Differential diagnosis

Authoritative Data Verified Data

take an appropriate amount of this product and the reference substance of irbesartan, add the mobile phase to dissolve and dilute to prepare a solution containing about 50ug each in 1 ml. According to the test method under the item of related substances, the retention time of the main peak of the test solution should be consistent with the retention time of the main peak of the control solution.
The infrared absorption spectrum of this product should be consistent with that of the control (Spectrum set 912).

Last Update：2022-01-01 11:32:09

Irbesartan Alkylation - Exam

Authoritative Data Verified Data

chloride

take 1.25g of this product, add 100ml of water, ultrasound, filter, take the filtrate 40ml, check according to law (General rule 0801), compared with the control solution made of standard sodium chloride solution, no more concentrated (0.006%).

sulfate

take this product l. Add 50ml of water, ultrasound, filter, take 25ml of filtrate, check according to law (General rule 0802), compared with the control solution made of 0.020% of standard potassium sulfate solution, not more concentrated ().

cyanide

take this product l.Og, inspection according to law (General Principles 0806 The first law), should comply with the provisions.

Related substances

take this product, precision weighing, adding methanol to dissolve and quantitatively dilute to make a solution containing about lmg per lml, as a test solution; Take lml for precision, set in a 200ml measuring flask, dilute to the scale with methanol, and shake to serve as a control solution. Precision weighing 1-(valerylamino) tetrazol-5-yl) biphenyl-4-yl] methyl] cyclopentane Formamide (impurity I) reference, methanol was added to dissolve and quantitatively diluted to prepare a solution containing about 1.5ug per 1 ml as a control solution. The appropriate amounts of irbesartan control and impurity I control were taken, dissolved and diluted with methanol to prepare a mixed solution containing about 0.1 mg each in 1 ml as a system applicable solution. According to the high performance liquid chromatography (General 0512) test, with eighteen alkyl silane bonded silica gel as filler, phosphoric acid solution (85% Phosphoric acid 5.5ml, add water to 3.2 ml, with triethylamine to adjust the pH value to)-Acetonitrile (62:38) as mobile phase, detection wavelength of 220mn. The applicable solution 10u1 of the system is injected into the liquid chromatograph, and the chromatogram is recorded. The separation degree of impurity I peak and irbesartan peak should be greater than 2.0, and the number of theoretical plates should not be less than 2000 based on irbesartan peak. The sample solution, the control solution and the reference solution were respectively 10 u1, and injected into the human liquid chromatograph respectively. The chromatogram was recorded to 3 times of the retention time of the main component peak. In the chromatogram of the test solution, if there is a chromatographic peak consistent with the retention time of impurity I, the peak area shall be calculated according to the external standard method, and shall not exceed 0.15%, the Peak area of other individual impurities shall not be greater than 0.2 times (0.1%) of the main peak area of the control solution, and the total amount of impurities shall not exceed 0.2%.

azide

take this product, precision weighing, add 90% methanol solution to dissolve and quantitatively dilute to make a solution containing about 20mg per 1 ml, as a test solution; Take the sodium azide reference substance, precision weighing, adding 90% methanol solution to dissolve and quantitatively dilute to make a solution containing about 0.312ug of sodium azide per 1 ml [equivalent to 0.2ug of azide (N3-) per 1 ml], as a reference solution; Take each appropriate amount of potassium bromide, sodium azide and potassium nitrate, add 90% methanol solution to dissolve and dilute to make a mixed solution containing about 0.2ug each in 1 ml as a system applicable solution. According to the ion chromatography (General 0513) test, use anion exchange chromatography column (IonPac AS18 column, or equivalent column), the detector is conductivity detector, and the detection method is suppressed conductivity detection, the column temperature was 30°C. Using potassium hydroxide solution as eluent, the analytical column concentration gradient was eluted according to the following procedure at a flow rate of 1.0 per minute. The on-line matrix elimination method with valve switching (see Appendix 2) is used for on-line treatment of the sample solution after injection. According to the above chromatographic conditions, take the applicable solution 200 u1 of the system and inject it into the ion Chromatograph. The separation degree of azide with bromide and nitrate should be greater than 1.5; 20 u1 of the test solution and the reference solution were respectively injected into the human ion chromatograph, and the chromatograms were recorded. If the azide peak is shown in the chromatogram of the test solution, the peak area shall be calculated according to the external standard method and shall not exceed 0.001%.

loss on drying

take this product, dry to constant weight at 105°C, weight loss shall not exceed 0.5% (General rule 0831).

ignition residue

l.Og of this product shall be taken for inspection according to law, and the residue left shall not exceed 0.1% (General rule 0841).

Heavy metals

The residue left under the item of burning residues shall be inspected according to law (General Principles 0821, Law II) and shall not contain more than 10 parts per million of heavy metals.

Last Update：2022-01-01 11:32:10

Irbesartan Alkylation - Content determination

Authoritative Data Verified Data

take this product 0.3g, precision weighing, add glacial acetic acid 20ml dissolved, add crystal violet indicator 1 drop, with perchloric acid titration solution (0.1 mol/L) titration to the solution shows blue color, and the titration result is corrected with blank test. Per 1 ml of perchloric acid titration solution (0.1 mol/L) corresponds to 42.85mg of C25H28N60.

Last Update：2022-01-01 11:32:10

Irbesartan Alkylation - Category

Authoritative Data Verified Data

antihypertensive drugs.

Last Update：2022-01-01 11:32:10

Irbesartan Alkylation - Storage

Authoritative Data Verified Data

sealed storage.

Last Update：2022-01-01 11:32:11

Irbesartan Alkylation - Lrbesartan Tablets

Authoritative Data Verified Data

This product contains Irbesartan (C25H28N6O) should be 95.0% to 105.0% of the label.

trait

This product is white or white-like tablets or film-coated tablets, white or white-like after removing the coating.

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 control solution.

examination

Related Substances: take the fine powder of this product, precisely weigh it, dissolve it with methanol and quantitatively dilute it to make a solution containing 1 mg of irbesartan per 1ml, filter it, and take the continued filtrate as the test solution; take 1ml of precision, 200ml flask, diluted with methanol to scale, shake, as a control solution. In addition, the reference substance of impurity I was accurately weighed, dissolved in methanol and quantitatively diluted to prepare a solution containing about 2ug per 1ml as a reference solution. According to the method of related substances of irbesartan. In the chromatogram of the test solution, in addition to the peak of the auxiliary material whose relative retention time of the main peak is less than 0.3 times, if there are chromatographic peaks with the same retention time as the impurity I peak, the peak area shall be calculated according to the external standard method, the Peak area of other individual impurities shall not be greater than 0.2% times (0.4) of the main peak area of the control solution, and the total amount of impurities shall not exceed 0.2%.
dissolution of this product, according to the dissolution and release determination method (General 0931 second method), with 0.900ml of 1 mol / L hydrochloric acid solution is the dissolution medium, and the rotation speed is 50 revolutions per minute, which is operated according to law. After 30 minutes, 10ml of the solution is filtered, and the appropriate amount of the filtrate is taken in a precise amount, A solution containing about 10 μg of irbesartan per 1 ml was prepared by quantitative dilution with the dissolution medium, and the absorbance was measured at a wavelength of 0401 NM according to ultraviolet-visible spectrophotometry (general rule). In addition, the appropriate amount of irbesartan reference substance was accurately weighed, dissolved and quantitatively diluted with dissolution medium to prepare a solution containing about lOug per 1 ml, and the dissolution amount of each tablet was calculated by the same method. The limit is 80% 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 eighteen alkyl silane bonded silica as filler, phosphoric acid solution (85% of 5.5 phosphoric acid, add water to 3.2 ml, adjust pH to with triethylamine)-Acetonitrile (62:38) as mobile phase, the detection wavelength was 245Nm. Take the appropriate amount of irbesartan control and impurity I control, respectively, and add methanol to dissolve and dilute to make each about 0 in 1 ml. lmg mixed solution, as the system applicable solution, take L01 injection liquid chromatograph, record chromatogram, peak order is impurity I peak and irbesartan peak, the degree of separation between the impurity I peak and the irbesartan peak should be greater than 2.0, and the theoretical plate number should not be less than 2000 based on the irbesartan peak.
determination of 20 tablets of this product, precision weighing, fine grinding, precision weighing an appropriate amount (equivalent to 10mg of irbesartan), put it in a 50ml measuring flask, add an appropriate amount of methanol, shake to dissolve irbesartan and dilute to the scale, shake well, filter, take the filtrate as a test solution, take the LOL into the liquid chromatograph, record the chromatogram; in addition, an appropriate amount of irbesartan reference substance was accurately weighed, dissolved in methanol and quantitatively diluted to make a solution containing 0.2 mg per 1 ml, which was determined by the same method. According to the external standard method to calculate the peak area, that is.

specification

(1)0.075g (2)0.15g (3)0.3g

storage

sealed storage.

Last Update：2022-01-01 11:32:12

Irbesartan Alkylation - Irbesartan dispersible tablets

Authoritative Data Verified Data

This product contains Irbesartan (C25H28N6O) should be 95.0% to 105.0% of the label.

trait

This product is white or off-white.

identification

examination

Related Substances: take the fine powder of this product, precisely weigh it, dissolve it with methanol and quantitatively dilute it to make a solution containing 1 mg of irbesartan per 1ml, filter it, and take the continued filtrate as the test solution; take 1ml of precision, 200ml flask, diluted with methanol to scale, shake, as a control solution. In addition, the reference substance of impurity I was accurately weighed, dissolved in methanol and quantitatively diluted to prepare a solution containing about 2ug per 1ml as a reference solution. According to the method of related substances of irbesartan. In the chromatogram of the test solution, in addition to the peak of the auxiliary material whose relative retention time of the main peak is less than 0.3 times, if there are chromatographic peaks with the same retention time as the impurity I peak, the peak area shall be calculated according to the external standard method, the Peak area of other individual impurities shall not be greater than 0.2% times (0.4) of the main peak area of the control solution, and the total amount of impurities shall not exceed 0.2%.
dissolution of this product, according to the dissolution and release determination method (General 0931 second method), with 0.900ml of 1 mol / L hydrochloric acid solution is the dissolution medium, and the rotation speed is 50 rpm, which is operated according to the law. After 20 minutes, 10ml of the solution is filtered, and the appropriate amount of the filtrate is taken in a precise amount, quantitative dilution with dissolution medium to make a solution containing about 1 ml of irbesartan lOug, UV-visible spectrophotometry (General rule 0401), the absorbance was measured at a wavelength of Nm. In addition, an appropriate amount of irbesartan reference substance was accurately weighed, dissolved and quantitatively diluted with dissolution medium to prepare a solution containing about 10ug per lml, and the dissolution amount of each tablet was calculated by the same method. The limit is 80% 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 with eighteen alkyl silane bonded silica gel as filler, with phosphoric acid solution (take 85% Phosphoric acid 5.5 ml, add water to 3.2 ml, with triethylamine to adjust the pH value to)-acetonitrile (62:38) as mobile phase, the detection wavelength was 245nm. Take the appropriate amount of irbesartan control and impurity I control, respectively, and add methanol to dissolve and dilute to prepare about irbesartan and impurity I per 1 ml. lmg mixed solution, as the system applicable solution, take 10u1 injection liquid chromatograph, record chromatogram, peak order is impurity I peak and irbesartan peak, the degree of separation between the impurity I peak and the irbesartan peak should be greater than 2.0, and the theoretical plate number should not be less than 2000 based on the irbesartan peak.
Determination of 20 tablets of this product, precision weighing, fine grinding, precision weighing an appropriate amount (approximately equivalent to irbesartan 10 mg ), 50 ml flask, add the appropriate amount of methanol, shake to dissolve irbesartan and dilute to the scale, shake well, filter, take the filtrate as a test solution, and inject 10ul into the liquid chromatograph to record the chromatogram; in addition, an appropriate amount of irbesartan reference substance was accurately weighed, dissolved in methanol and quantitatively diluted to make a solution containing 0.2mg per 1 ml, which was determined by the same method and calculated by peak area according to external standard method.

specification

(1)0.075g (2)0.15g

storage

sealed storage.

Last Update：2022-01-01 11:32:12

Irbesartan Alkylation - Irbesartan Capsules

Authoritative Data Verified Data

This product contains Irbesartan (C25H28N6O) should be 95.0% to 105.0% of the label.

trait

The contents of this product are white or off-white powder or granules.

identification

examination

The fine powder under the content determination item of related substances is accurately weighed, dissolved with methanol and quantitatively diluted to prepare a solution containing about 1 mg of irbesartan per 1ml, filtered, the filtrate was taken as a test solution; 1ml was accurately measured, placed in a 200ml measuring flask, diluted to a scale with methanol, and shaken to obtain a control solution. In addition, an appropriate amount of the reference substance of impurity I was accurately weighed, dissolved in methanol and quantitatively diluted to prepare a solution containing about 2ug per 1ml as a reference solution. According to the method of related substances of irbesartan. In the chromatogram of the test solution, in addition to the peak of the auxiliary material whose relative retention time of the main peak is less than 0.3 times, if there are chromatographic peaks with the same retention time as the impurity I peak, the peak area shall be calculated according to the external standard method, the Peak area of other individual impurities shall not be greater than 0.2% times (0.4) of the main peak area of the control solution, and the total amount of impurities shall not exceed 0.2%.
dissolution: according to the method of dissolution and release determination (General rule 0931, second method), ML of 0.lmol/L hydrochloric acid solution was used as the dissolution medium, and the rotation speed was 50 rpm, operate in accordance with the law, after 30 minutes, take 10ml of the solution for filtration, take the appropriate amount of the filtrate with precision, and dilute quantitatively with the dissolution medium to make a solution containing about 10 μl of irbesartan per 1 ml, the absorbance was measured at a wavelength of 0401 NM according to UV-Vis spectrophotometry (general rule). In addition, the appropriate amount of irbesartan reference substance was accurately weighed, dissolved and quantitatively diluted with dissolution medium to prepare a solution containing about 10ul per lml. The same method was used to determine and calculate the dissolution amount of each particle, the limit is 80% 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 eighteen alkyl silane bonded silica as filler, phosphoric acid solution (85% of 5.5 phosphoric acid, add water to 3.2 ml, adjust pH to with triethylamine)-Acetonitrile (62:38) as mobile phase, detection wavelength of 245mn. Take the appropriate amount of irbesartan control and impurity I control, respectively, and add methanol to dissolve and dilute to prepare about irbesartan and impurity I per 1 ml. lmg mixed solution, as the system applicable solution, 10u1 was injected into the liquid chromatograph, and the chromatogram was recorded. The order of peaks was impurity I peak and irbesartan peak, the degree of separation between the impurity I peak and the irbesartan peak should be greater than 2.0, and the theoretical plate number should not be less than 2000 based on the irbesartan peak.
the content under the item of loading amount difference was measured, ground finely, and an appropriate amount (equivalent to 10mg of irbesartan) was accurately weighed, placed in a 50ml measuring flask, and the appropriate amount of methanol was added, shake to dissolve irbesartan and dilute to the scale, shake, filter, take the filtrate as a test solution, take the LOL injection liquid chromatograph, record the chromatogram; in addition, an appropriate amount of irbesartan reference substance was accurately weighed, dissolved in methanol and quantitatively diluted to make a solution containing 0.2 mg per 1 ml, which was determined by the same method and calculated by peak area according to external standard method.