morphinan-6-one,4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-,hydrochloride,(5-a
naloxone hydrochloride
CAS: 357-08-4
Molecular Formula: C19H22ClNO4
morphinan-6-one,4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-,hydrochloride,(5-a - Names and Identifiers
| Name | naloxone hydrochloride |
| Synonyms | en1530 Naloxone HCl NALOXONE HCL NALOXONE HYDROCHLORIDE naloxone hydrochloride l-n-allyl-14-hydroxynordihydromorphinonehydrochloride 17-allyl-4,5-alpha-epoxy-3,14-dihydroxymorphinan-6-onehydrochloride 4,5alpha-epoxy-3,14-dihydroxy-17-(2-propenyl)morphinan-6-one hydrochloride (5ALPHA)-4,5-EPOXY-3,14-DIHYDRO-17-(2-PROPENYL)MORPHINAN-6-ONE HYDROCHLORIDE morphinan-6-one,4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-,hydrochloride,(5-a (5alpha)-3,14-dihydroxy-17-prop-2-en-1-yl-4,5-epoxymorphinan-6-one hydrochloride |
| CAS | 357-08-4 |
| EINECS | 206-611-0 |
| InChI | InChI=1/C19H21NO4.ClH/c1-2-8-20-9-7-18-15-11-3-4-12(21)16(15)24-17(18)13(22)5-6-19(18,23)14(20)10-11;/h2-4,14,17,21,23H,1,5-10H2;1H/t14-,17+,18+,19-;/m1./s1 |
morphinan-6-one,4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-,hydrochloride,(5-a - Physico-chemical Properties
| Molecular Formula | C19H22ClNO4 |
| Molar Mass | 363.84 |
| Melting Point | 200-2050C |
| Boling Point | 532.8°C at 760 mmHg |
| Flash Point | 276.1°C |
| Water Solubility | Soluble in water (73 mg/ml), ethanol (3.3 mg/ml), methanol (50 mg/ml) and dimethyl sulfoxide (73 mg/ml). Insoluble in ether |
| Solubility | ethanol: 3.3mg/mL stable for several months refrigerated if protected from light. |
| Vapor Presure | 3.49E-12mmHg at 25°C |
| Appearance | powder |
| Color | white to off-white |
| Storage Condition | 2-8°C |
| Stability | Stable for 1 year from date of purchase as supplied. Solutions in DMSO or distilled water may be stored at -20°C for up to 2 months. |
| Physical and Chemical Properties | Crystallization. Melting point 200-205 °c. Soluble in water, alcohol, insoluble in ether. Naloxone ([465-65-6]) m. P. 184 °c. |
| Use | Morphine antagonists for acute poisoning of morphine |
| In vitro study | Naloxone significantly reduced the LPS-induced degeneration of midbrain neurons. The dopaminergic neurons protected by Naloxone and the stereoisomer (+)- Naloxone had equal potency. Naloxone inhibits LPS-induced microglial activation and the release of inflammatory factors, and inhibits the production of superoxide free radicals by microglia, which has the best correlation with the protective effect of Naloxone isomers. Naloxone partially inhibits the binding of [(3)H] LPS to the cell membrane, but has no effect on the loss of dopaminergic neurons caused by Peroxynitrite, a product of nitric oxide and superoxide. |
| In vivo study | Naloxone(18.0 mg/kg) inhibited water intake in rats when water was used as the sole fluid source. When rats had a free choice between an ethanol solution and water, Naloxone dose-dependently reduced ethanol consumption without altering water intake. In beer-drinking and near-beer-drinking rats, Naloxone(10 mg/kg) caused a dose-dependent decrease in breakpoint and locomotor activity in the substantia nigra of rats, naloxone inhibited LPS-induced activation of microglia and significantly reduced LPS-induced loss of dopaminergic neurons. N In both hot-plate and formalin tests, Naloxone inhibited this analgesic activity without affecting plasma levels of acetaminophen. Naloxone prevents an increase in the concentration of 5-HT in the central nervous system and a decrease in 5-HT2 receptors in the cortical membranes. |
morphinan-6-one,4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-,hydrochloride,(5-a - Risk and Safety
| Hazard Symbols | Xi - Irritant |
| Risk Codes | 36/37/38 - Irritating to eyes, respiratory system and skin. |
| Safety Description | S22 - Do not breathe dust. S24/25 - Avoid contact with skin and eyes. S26 - In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. S36/37/39 - Wear suitable protective clothing, gloves and eye/face protection. S36 - Wear suitable protective clothing. |
| WGK Germany | 3 |
| RTECS | QD2275000 |
morphinan-6-one,4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-,hydrochloride,(5-a - Standard
Authoritative Data Verified Data
This product is 17-allyl -4, 5a-epoxy-3, 14-dihydroxymorphin-6-one hydrochloride dihydrate. The content of C19H21N04 • HC1 shall be between 98.0% and 102.0% calculated as dry.
Last Update：2024-01-02 23:10:35
morphinan-6-one,4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-,hydrochloride,(5-a - Trait
Authoritative Data Verified Data
- This product is white crystal or crystalline powder; Odorless.
- This product is soluble in water, soluble in methanol, almost insoluble in chloroform or ether.
specific rotation
take this product, precision weighing, add water to dissolve and quantitatively dilute to make a solution containing about 25mg per lml, and determine according to law (General rule 0621), the specific rotation was -170 ° to -181 °.
Last Update：2022-01-01 15:05:24
morphinan-6-one,4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-,hydrochloride,(5-a - Differential diagnosis
Authoritative Data Verified Data
- take about 2mg of this product, put it in a small test tube, add 3-4 drops of citric acid acetic anhydride test solution, and heat it in a water bath at 80-90°C for 3-5 minutes to show purplish red color.
- take about 1 mg of this product, add 1 ml of water to dissolve, add 1 drop of dilute potassium ferricyanide test solution, which shows blue-green color.
- when dried to constant weight at 105°C, the infrared absorption spectrum of the product should be consistent with that of the control (Spectrum set 646).
- This product is chloride identification reaction (General 0301).
Last Update：2022-01-01 15:05:24
morphinan-6-one,4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-,hydrochloride,(5-a - Exam
Authoritative Data Verified Data
chlorine content
take this product about 0.30g, precision weighing, add methanol 30ml dissolved, add water 5ml and fluorescent yellow indicator liquid 6~7 drops, with silver nitrate titration solution (O. 1 mol/L) titration to the solution is pink. Each 1 ml of silver nitrate titration solution (0.1 mol/L) corresponds to 3.545mg of C1. The chlorine content shall be 9.54%-9.94% based on the dry product.
Related substances
take this product, precision weighing, add 0.1 mol/L hydrochloric acid solution dissolved and quantitatively diluted to prepare a solution containing about 5mg per 1ml as a test solution; Take (1)-4,5a-epoxy -3,14-dihydroxymorphinin-6-one control (impurity I) appropriate amount, precision weighing, add 0.1 mol/L hydrochloric acid solution is dissolved and quantitatively diluted to prepare a solution containing about 1 mg per 1 ml, which is used as a reference solution; 1ml of the test solution and 5ml of the reference solution are accurately measured, in the same 200ml measuring flask, use 0.1 mol/L hydrochloric acid solution was diluted to the scale and shaken to serve as a control solution. Take the right amount of naloxone hydrochloride control, add 0.1 mol/ L hydrochloric acid solution is dissolved and made into a solution containing about 0.2mg per lml, take 10ml into a 25ml measuring flask, add 1ml of 0.4% ferric chloride solution, heat it in a water bath for 10 minutes, and let it cool, dilute to scale with water and shake well as a system-suitable solution containing 2,2 '-dinaloxone (impurity n). Test according to high performance liquid chromatography (General 0512). The mobile phase A was acetonitrile-tetrahydrofuran -5mmol/L sodium octane sulfonate solution (adjusted to pH 2.0 with phosphoric acid) (20:40:940), the mobile phase B was acetonitrile-tetrahydrofuran-5 mmol/L sodium octane sulfonate solution (adjusted to pH 2.0 with phosphoric acid)(255:60:685), followed by gradient elution; the flow rate was 1.5ml per minute; The detection wavelength was 230nm; And the column temperature was 40°C. The system applicable solution lOpl is injected into the liquid chromatograph, and the peak order is naloxone and impurity II, and the retention time of naloxone peak is about 14 minutes, the separation degree of impurity I peak and naloxone peak should be greater than 4.0, and 10 u1 of the control solution and the test solution should be accurately measured and injected into the liquid chromatograph respectively to record the chromatogram. If there are chromatographic peaks consistent with retention time of impurity I in the chromatogram of the test solution, the peak area shall not exceed 0.5% based on the external standard method; If there are chromatographic peaks consistent with retention time of impurity II, the peak area shall be multiplied by the correction factor of 0.53, and shall not be greater than the peak area of naloxone in the control solution (0.5%); The peak area of other individual impurities shall not be greater than the peak area of naloxone in the control solution (0.5%); the sum of each impurity peak area shall not be greater than 2 times (1.0%) the area of the naloxone peak in the control solution. The chromatogram of the test solution is 0.05 times smaller than the naloxone peak area in the control solution.
loss on drying
take 0.5g of this product, first dry at 90°C for 4 hours, then dry at 105°C to constant weight, and lose no more than 11.0% of weight (General rule 0831).
Last Update：2022-01-01 15:05:25
morphinan-6-one,4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-,hydrochloride,(5-a - Content determination
Authoritative Data Verified Data
take this product about 0.2g, precision weighing, add glacial acetic acid 40ml and acetic anhydride 10ml ultrasonic to dissolve, let cool, according to the potential titration method (General 0701), with perchloric acid titration solution (0.1 mol/L) titration, and the results of the titration were corrected with a blank test. Each 1 ml perchloric acid titration solution (0.1 mol/L) corresponds to 36.38mg of C19H21N04. HCl.
Last Update：2022-01-01 15:05:26
morphinan-6-one,4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-,hydrochloride,(5-a - Category
Authoritative Data Verified Data
morphine antagonists.
Last Update：2022-01-01 15:05:26
morphinan-6-one,4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-,hydrochloride,(5-a - Storage
Authoritative Data Verified Data
light shielding, sealed storage.
Last Update：2022-01-01 15:05:26
morphinan-6-one,4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-,hydrochloride,(5-a - Naloxone hydrochloride injection
Authoritative Data Verified Data
This product is a sterile aqueous solution of naloxone hydrochloride. The content of naloxone hydrochloride (C19H21N04 • HCl) shall be between 90.0% and 110.0% of the labeled amount.
trait
This product is colorless and clear liquid.
identification
- take an appropriate amount of this product, put it in a porcelain evaporation dish, evaporate it in a boiling water bath, add 1 drop of citric acid acetic anhydride test solution, and heat it in a water bath at 80-90°C for 3-5 minutes to show a purple-red color.
- take this product, according to UV-visible spectrophotometry (General rule 0401), there is maximum absorption at the wavelength of 280nm, there is minimum absorption at the wavelength of 263nm.
- 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.
examination
- the pH value should be 3.0 to 4.0 (General 0631).
- impurity I take the test solution under the content determination item as the test solution; Take 1ml for precise measurement, put it in a 50ml measuring flask, dilute it to the scale with water, and shake it well, as a control solution; Take an appropriate amount of naloxone hydrochloride control, add 0.1mol/L hydrochloric acid solution to dissolve and make a solution containing 0.2mg per 1ml, take 10ml, put it in a 25ml measuring flask, add 1ml of 0.4% ferric chloride solution, heat in a water bath for 10 minutes, let cool, dilute to the mark with water, and shake well as a system-suitable solution containing impurity II. According to the chromatographic conditions under the content determination item, 10ul of the applicable solution of the system is injected into the liquid chromatograph, and the order of peaks is naloxone hydrochloride and impurity II; the control solution and the test solution were respectively injected with human liquid chromatography, and the chromatograms were recorded. If there are chromatographic peaks in the chromatogram of the test solution that are consistent with the retention time of impurity II, the peak area shall be multiplied by the correction factor of 0.53, and shall not be greater than 2 times (4.0%) of the main peak area of the control solution.
- bacterial endotoxin take this product, according to the law inspection (General 1143), each 1 mg naloxone hydrochloride containing endotoxin amount should be less than 25EU.
- others should comply with the relevant provisions under injection (General 0102).
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 sodium octane sulfonate solution (1-octane sodium sulfonate 1.36g and sodium chloride l. The mixture was dissolved in 580ml of water and then shaken with methanol-phosphoric acid (420:: 1) as the mobile phase. The detection wavelength was at 229nm. The number of theoretical plates is not less than 1000 based on the naloxone peak.
- determination precision take appropriate amount of this product, with diluent (take ethylenediamine tetraacetic acid disodium 150mg, put 2000ml measuring flask, add hydrochloric acid 0.9ml, add water to dissolve and dilute to the scale, shake well) the quantitative dilution is made to contain about naloxone hydrochloride in each 1 ml. lmg solution, as a test solution, take 10u1 injection liquid chromatograph for precise measurement, record chromatogram; Take naloxone hydrochloride reference substance, precision weighing, and operate with the same method. According to the external standard method to calculate the peak area, that is.
category
Same as naloxone hydrochloride.
specification
(1)lml:0.4mg (2)lml:lmg (3)2ml:2mg (4) 10ml:4mg
storage
sealed and preserved in a dry place.
Last Update：2022-01-01 15:05:27
morphinan-6-one,4,5-epoxy-3,14-dihydroxy-17-(2-propenyl)-,hydrochloride,(5-a - Naloxone Hydrochloride For Injection
Authoritative Data Verified Data
This product is a sterile freeze-dried product of naloxone hydrochloride. The content of naloxone hydrochloride (C19H21N04 • HCl) shall be between 95.0% and 105.0% of the labeled amount.
trait
This product is white or off-white loose block or powder.
identification
- take an appropriate amount of this product (about 1 mg equivalent to naloxone hydrochloride), add 1 ml of water to dissolve, add 1 drop of potassium ferricyanide test solution, which shows blue-green color.
- 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 aqueous solution of this product was chloride identification (1) of the reaction (General 0301).
examination
- acidity: Take appropriate amount of this product, add water to dissolve and make a solution containing 0.4mg per lml, and measure according to law (General rule 0631). The pH value should be 3.0~7.0.
- the clarity and color of the solution take an appropriate amount of this product, add water to dissolve and make a solution containing 0.4mg per 1 ml, the solution should be clear and colorless; If it is turbid, it shall not be more concentrated than the turbidity standard liquid No. 1 (General rule 0902 method 1); In case of color development, it shall not be deeper than the yellow Standard Colorimetric liquid No. 1 (General rule 0901 method 1).
- relevant substances take appropriate amount of this product, precision weighing, add 0.1 mol/L hydrochloric acid solution was dissolved and quantitatively diluted to prepare a solution containing about 0.4mg of naloxone hydrochloride per 1ml as a test solution. 1 mol/L hydrochloric acid solution is dissolved and quantitatively diluted to make a solution containing about 0.4mg per 1ml, which is used as a reference solution; 1ml of each of the test solution and the reference solution is accurately measured, in the same 200ml measuring flask, use 0.1 mol/L hydrochloric acid solution was diluted to the scale and shaken to serve as a control solution. Take the right amount of naloxone hydrochloride control, add 0.1 mol/L hydrochloric acid solution is dissolved and diluted to make a solution containing about 0.2mg per lml, take 10ml into a 25ml measuring flask, add 1ml of 0.4% ferric chloride aqueous solution, heat it in a water bath for 10 minutes, and let it cool, dilute to scale with water and shake well as a system-suitable solution containing naloxone hydrochloride impurity II. According to the chromatographic conditions under naloxone hydrochloride related substances, take the system applicable solution 50 u1 and inject it into the liquid chromatograph. The order of peaks is naloxone peak and impurity II peak, the retention time of the naloxone peak was approximately 20 minutes. The control solution 50u1 is injected into the liquid chromatograph, and the separation degree of the impurity I peak and the naloxone peak should be greater than 4.0. The control solution and the test solution 50 u1 were respectively injected into the human liquid chromatograph, and the chromatograms were recorded. If there is a chromatographic peak in the chromatogram of the test solution that is consistent with the retention time of impurity I, the peak area shall be calculated according to the external standard method, and 0.5% of naloxone hydrochloride shall not be passed; If there is a chromatographic peak that is consistent with the retention time of impurity II, the peak area is multiplied by the correction factor of 0.53, and shall not be greater than the naloxone peak area in the control solution (0.5% ) ; Other individual impurity peak area (except for the peak before the relative retention time of 0.2) the Peak area of naloxone in the control solution shall not be greater than (0.5% ) ; The sum of the peak areas of each impurity shall not be greater than 4 times (2.0%) The Peak area of naloxone in the control solution. The chromatogram of the test solution is 0.05 times smaller than the naloxone peak area in the control solution. The content uniformity of
- shall be calculated based on the content of each bottle measured under the content determination item, and shall comply with the regulations (General rule 0941).
- the moisture content of this product shall not exceed 0832 as determined by the method for determination of moisture (General rule 4.0%, first method 1).
- bacterial endotoxin take this product, according to the determination (General 1143), each 1 mg naloxone hydrochloride containing endotoxin amount should be less than 30EU.
- others should comply with the relevant provisions under injection (General 0102).
Content determination
- measured by high performance liquid chromatography (General 0512).
- chromatographic conditions and system suitability test using octyl silane bonded silica gel as filler; 5 mmol / L sodium octane sulfonate solution (adjusted to pH 2.0 with phosphoric acid)-Acetonitrile-tetrahydrofuran (800:255:60) as mobile phase; The detection wavelength was 230nm. The number of theoretical plates should not be less than 2000 based on the calculation of naloxone peak.
- determination Method: Take 10 bottles of this product and add 0. The lmol/L hydrochloric acid solution is dissolved and quantitatively diluted to make a solution containing about 40ug of naloxone hydrochloride in each lml, which is used as a sample solution, and 20ul is accurately measured and injected into the human liquid chromatograph, and the chromatogram is recorded; an appropriate amount of naloxone hydrochloride reference substance was added, and the procedure was the same. According to the external standard method, the content of each bottle is calculated by Peak area, and the average content of 10 bottles is calculated.
category
Same as naloxone hydrochloride.
specification
(1)0.4mg (2)0.8mg (3)1.Omg (4)1.2mg(5)2.Omg (6)4.Omg
storage
light shielding, closed storage.
Last Update：2022-01-01 15:05:29
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