Name | bezafibrate |
Synonyms | bezafibrat bezafibrate bezafibrato Benzafibrate Bezafibrate-d6 Lysolecithin, hydrogenated Bezabrate D6 (DiMethyl D6) Bezafibrate D6 (dimethyl D6) BEZAFIBRATE MM(CRM STANDARD) BEZAFIBRATE EPB(CRM STANDARD) 2-(4-{2-[(4-chlorobenzoyl)amino]ethyl}phenoxy)-2-methylpropanoic acid 2-(4-{2-[(4-chlorophenyl)forMaMido]ethyl}phenoxy)-2-Methylpropanoic acid |
CAS | 41859-67-0 |
EINECS | 255-567-9 |
InChI | InChI=1/C19H20ClNO4/c1-19(2,18(23)24)25-16-9-3-13(4-10-16)11-12-21-17(22)14-5-7-15(20)8-6-14/h3-10H,11-12H2,1-2H3,(H,21,22)(H,23,24) |
Molecular Formula | C19H20ClNO4 |
Molar Mass | 361.82 |
Density | 1.260±0.06 g/cm3(Predicted) |
Melting Point | 184 °C |
Boling Point | 572.1±45.0 °C(Predicted) |
Flash Point | 299.8°C |
Solubility | DMF: soluble |
Vapor Presure | 6.29E-14mmHg at 25°C |
Appearance | solid |
Color | White to Off-White |
Merck | 14,1195 |
pKa | 3.29±0.10(Predicted) |
Storage Condition | 2-8°C |
Stability | Hygroscopic |
Refractive Index | 1.583 |
Use | Phenoxyaromatic acid hypolipidemic drugs, and antithrombotic effect |
In vitro study | Bezafibrate is a lipid-lowering Fibric acid derivative. The EC50 of Bezafibrate bound to xPPAR β was 5 μm. Bezafibrate transcriptionally activates PPAR beta of Xenopus with an EC50 of 1 μm. Primary culture of Rat Adipocytes for 24 hours in the presence of Bezafibrate was able to increase the mRNA levels of key genes involved in peroxisomal and mitochondrial β-oxidation. The levels of mRNA of the rate-limiting enzymes of peroxisomal β-oxidation, acyl-CoA oxidase and muscle-type carnitine palmitoyltransferase I (M-CPT-I), were increased 1.6-and 4.5-fold, respectively. Bezafibrate induced an increase in uncoupling protein -2 (UCP-2; 1.5-fold induction) and UCP-3 (3.7-fold induction) transcripts mitochondrial proteins, while decreasing ATP yield and possibly promoting fatty acid oxidation. In addition, Bezafibrate also increased mRNA levels of fatty acid translocase (2-fold induction). Bezafibrate was able to elicit a 1.9-fold induction of 9,10-[ |
In vivo study | Bezafibrate treatment was able to induce an increase in the mRNA levels of M-CPT-I (4.5-fold induction), fatty acid translocase (2.6-fold induction) and Pref-1 (5.6-fold induction) in rat epididymal white adipose tissue.. Compared with the control group, the administration of Bezafibrate caused a significant increase in liver weight in wild-type and PPARβ-null mice, while the administration of Bezafibrate in PPARα-null mice showed no change in liver weight. In wild-type and PPARβ-null mice given Bezafibrate, gonadal fat stores were much smaller than in the control group (2.8-fold and -2.6-fold less, respectively), this effect was not found in PPARα-null mice fed the same way. Compared with the control group, Bezafibrate is able to cause mRNAs encoding lipid metabolism enzymes (such as AOX , cytochrome P450 4A (CYP4A), LPL, ACS, and LCA D) changes. Bezafibrate can induce the expression of UCPs in rat epididymal white adipose tissue, and can change the energy balance by directly inducing the expression of aco gene (14.5-fold on day 7) and peroxisomal fatty acid β-oxidation. In addition, Bezafibrate significantly reduced plasma triglyceride and leptin concentrations without modifying white adipose tissue PPAR gamma levels or the ob gene. |
Hazard Symbols | Xn - Harmful |
Risk Codes | 22 - Harmful if swallowed |
Safety Description | 36 - Wear suitable protective clothing. |
WGK Germany | 1 |
RTECS | UE8755000 |
HS Code | 29242990 |
Toxicity | LD50 oral in rat: 1082mg/kg |
This product is 2-[4-[2-(4-chlorobenzoylamino) ethyl] phenoxy]-2-methylpropionic acid. Calculated as dried product, the content of C19H20C1N04 shall not be less than 98.5%.
The melting point of this product (General 0612) is 180~184°C.
take 0.50g of this product, put it in a 50ml measuring flask, Add 10ml of N-dimethylformamide to dissolve it, dilute it with water to the scale, shake it, filter it in a precise amount, and take 15ml of continued filtrate, put 50ml Nessler's colorimetric tube, add water to make 25ml, check according to law (General rule 0801), and standard sodium chloride solution 5.0ml compared with 0.03% ml of control solution made of N,N-dimethylformamide, no more ().
take this product, add the mobile phase to dissolve and dilute to make a solution containing about 0.5mg per 1 ml, as the test solution; Take the sample to dissolve 1 ml, put it in a 100ml measuring flask, dilute to the scale with the mobile phase and shake well as a pair of solutions. According to the high performance liquid chromatography (General 0512) test, using the eighteen alkyl silicon bonded silica gel as filler; With 0.Olmol/L potassium dihydrogen phosphate solution (pH value to 3.8 with phosphoric acid)-methanol (40:60) as mobile phase; The mobile phase ratio can be adjusted so that the retention time of bezafibrate peak is 6-10 minutes; the detection wavelength was 228nm. Bezafibrate control and N-(4-chlorobenzoyl)-tyramine (hetero-I) control were dissolved and diluted with mobile phase to make 0.lmg solution, as the system applicable solution, take 20 u1, inject human liquid chromatograph, record chromatogram, the separation degree of bezafibrate peak and impurity I peak should be greater than 5.0, the number of theoretical plates is not less than 3000 based on the bezafibrate peak. Accurately take 20 u1 of each of the supply solution and the control solution, respectively inject into the liquid chromatograph, record the chromatogram to 4 times of the retention time of the main component peak, if there are impurity peaks in the chromatogram of the test solution, the single impurity peak area shall not be greater than 0.5 times (0.5%) of the main peak area of the control solution, and the sum of each impurity peak area shall not be greater than 0.75 times (0.75%) of the main peak area of the control solution.
weigh 0.50g of this product accurately, place it in the top empty bottle, add 5ml of N,N-dimethylformamide accurately to dissolve it, and use it as the test solution, N,N-dimethylformamide was added to dissolve and dilute to prepare a solution containing about 6ug per 1 ml as a control solution. Test as residual solvent assay (General 0861 second method). With 5% diphenyl-95% dimethyl siloxane copolymer (or polar similar) as stationary liquid; The initial temperature is 50 °, maintained for 5 minutes, and the temperature is raised to 175 ° C at a rate of 8 ° C per minute, maintained for 3 minutes; the inlet temperature was 120°C; The detector temperature was 250°C; The headspace bottle equilibration temperature was 85°C and the equilibration time was 30 minutes. The test solution and the reference solution were injected by Headspace, and the chromatograms were recorded. According to the external standard method to calculate the peak area, the residual amount of chloroform should comply with the provisions.
take this product, dry to constant weight at 105 °, weight loss shall not exceed 1.0% (General rule 0831).
take l.Og of this product and check it according to law (General rule 0841). The residue left shall not exceed 0.1%.
The residue left under the item of taking the ignition residue shall not contain more than 10 parts per million of heavy metal when examined by law (General Principles 0821, Law II).
take about 0.4g of this product, weigh it accurately, add 50ml of neutral ethanol (neutral to phenolphthalein indicator solution), heat and dissolve it in a warm water bath, then cool it to room temperature, phenolphthalein indicator solution 3 drops, with sodium hydroxide titration solution (0.05mol/L) titration. Each 1 ml of sodium hydroxide titration solution (0.05mol/L) corresponds to 18.09mg of Cl9H20ClN04.
hypolipidemic drugs.
sealed storage.
This product contains bezafibrate (C19H20C1N04) should be 90.0% to 110.0% of the label.
This product is white or white-like tablets or film-coated tablets, white or white-like after removing the coating.
Take 20 tablets of this product, precision weighing, fine grinding, precision weighing take appropriate amount (about equivalent to bezafibrate O.lg ), put it in a 100ml measuring flask, add an appropriate amount of phosphate buffer (pH 7.6), shake, dissolve bezafibrate and dilute to the scale, shake well, filter, and take an appropriate amount of filtrate accurately, A solution containing about 10mg bezafibrate per 1 ml was prepared by quantitative dilution with phosphate buffer solution (pH 7.6), and the absorbance was measured by ultraviolet-visible spectrophotometry (General 0401) at the wavelength of 228mn; another reference substance of bezafibrate was precisely weighed, dissolved and quantitatively diluted with phosphate buffer (pH 7.6) to prepare a solution containing about 10ug per 1 ml, which was determined by the same method and calculated by peak area according to external standard method.
with Bezafibrate.
0.2g
sealed and stored in a cool and dry place.
This product contains bezafibrate (C19H20C1N04) should be 90.0% to 110.0% of the label.
The content of this product is white particles or powder.
take the contents under the difference of loading amount, grind them finely, mix them evenly, weigh an appropriate amount (about 10mg equivalent to bezafibrate) precisely, put them in a 100ml measuring flask, and add phosphate buffer (pH 7.6). Appropriate amount, shake, dissolve bezafibrate and dilute to the scale, shake, filter, take the appropriate amount of filtrate, with phosphate buffer (pH 7.6) A solution containing about 10 WDS of bezafibrate per lm l was prepared by quantitative dilution, and the absorbance was measured at the wavelength of 228nm by UV-Vis spectrophotometry (General rule 0401 ), precision weighing, plus phosphate buffer solution (pH 7.6) dissolved and quantitatively diluted to prepare about 10 mL solution per lm l, the same method of determination, calculation, that is.
with Bezafibrate.
0.2g
sealed and stored in a cool and dry place.