Molecular Formula | C24H32N2O9 |
Molar Mass | 492.52 |
Melting Point | 143-144,5°C |
Boling Point | 0°C |
Specific Rotation(α) | D25 -42.2° (c = 1 in methanol) |
Flash Point | 0°C |
Water Solubility | Soluble in water, methanol, and ethanol. |
Solubility | Soluble in water (25 mg/ml), methanol (50 mg/ml), and ethanol (8 mg/ml). |
Vapor Presure | 1.25E-24mmHg at 25°C |
Appearance | White crystalline powder |
Color | white to off-white |
Maximum wavelength(λmax) | ['208nm(MeOH)(lit.)'] |
Merck | 14,3567 |
pKa | pKa1 3.0; pKa2 (25°) 5.4 |
Storage Condition | 2-8°C |
MDL | MFCD00133304 |
Physical and Chemical Properties | White crystalline powder. The melting point was 140-147 °c. |
Use | For renin-angiotensin antihypertensive drugs |
In vitro study | Enalapril is rapidly converted by ester hydrolysis to enalaprilat, a potent ACE inhibitor; Enalapril itself is only a weak ACE inhibitor. Enalapril reduces peripheral vascular resistance without increasing heart rate. |
In vivo study | In nnee mice, Enalapril blocks the deleterious effects of eNOS deficiency on blood pressure (BP), atherosclerosis, and renal insufficiency. In mdx mice, Enalapril caused a dose-dependent increase in forelimb strength. In the tibialis anterior muscle of mdx mice, Enalapril dose-dependently decreases superoxide anion production, as observed by dihydro-ethiene staining. Enalapril(5 mg/kg) reduced necrosis in both gastrocnemious muscle and septal muscle areas, while had no significant effect on non-muscle areas. In rats with bacterin (STZ)-induced diabetes (STZ-DM), Enalapril significantly increases kidney weight and urinary albumin concentration, as a result of Enalapril maleate, N-acetyl-FL-D-glucosamidase(NAG) and ET-1 in serum, and the concentration of ET-1 in the kidneys tends to increase. In the kidneys of diabetic rats, Enalapril caused increased mesangial cell proliferation, stromal expansion, and enlargement of the mesangial zone. In STZ-DM rats, Enalapril decreased increased urinary albumin and NAG concentrations, with slight improvement in electron microscopic changes. |
Risk Codes | R36/37/38 - Irritating to eyes, respiratory system and skin. R62 - Possible risk of impaired fertility R63 - Possible risk of harm to the unborn child |
Safety Description | S22 - Do not breathe dust. S24/25 - Avoid contact with skin and eyes. S36/37 - Wear suitable protective clothing and gloves. S26 - In case of contact with eyes, rinse immediately with plenty of water and seek medical advice. |
UN IDs | 3077 |
WGK Germany | 2 |
RTECS | TW3666000 |
HS Code | 29339900 |
Toxicity | LD50 oral in rat: 2973mg/kg |
This product is N-[(S) -1-ethoxycarbonyl-3-phenylpropyl]-L-alanyl-L-proline maleate. Calculated as dry product, containing C20H28N2O5 • C4H404 shall not be less than 98.5%.
take this product, precision weighing, add methanol to dissolve and quantitative dilution to make a solution containing about 50mg per lml, according to the law (General 0621), the specific rotation is from -41.0°C to -43.5°C.
take this product O.lg, add water 10ml to dissolve, according to the law (General 0631),pH value should be 2.0~2.8.
take this product, add the mobile phase to dissolve and dilute to make a solution containing about 2mg per 1 ml, as a test solution; Take the appropriate amount of precision, quantitative dilution with mobile phase to prepare a solution containing about 20ug per lml as a control solution; Appropriate amount of maleic acid was taken, and the mobile phase was added to dissolve and dilute to prepare a solution containing about 0.5mg per lml; in addition, appropriate amounts of the enalaprilat (impurity I) control, the enalapril maleate control and the enalapril Dione (impurity II) control were separately taken, and the mobile phase was added to dissolve and dilute to prepare a mixed solution containing about 20ug each in 1 ml. According to the high performance liquid chromatography (General 0512) test, using octanosilane bonded silica gel as filler, phosphate buffer solution (0.Olmol / L potassium dihydrogen phosphate solution, adjusted to pH 2.2 with phosphoric acid)-acetonitrile (75:25) as mobile phase; The detection wavelength was 215nm; The column temperature was 50°C. Take 20 u1 of maleic acid solution and mixed solution, respectively inject human liquid chromatograph, record chromatogram, peak order: maleic acid peak, impurity I Peak, enalapril peak and impurity II peak, the tailing factor of enalapril peak should be less than 2.0, the separation degree between maleic acid peak and impurity I peak should meet the requirements, and the separation degree between impurity I Peak, enalapril peak and impurity II peak should be greater than 4.0. Accurately take 20 u1 of the test solution and the control solution respectively, inject them into the liquid chromatograph, record the chromatogram until the peak of impurity II is finished. If there is any impurity peak in the chromatogram of the test solution, the Peak area of individual impurities shall not be greater than 0.3 times (0.3%) The Peak area of enalapril in the control solution, and the sum of the peak areas of each impurity shall not be greater than the peak area of enalapril in the control solution (1.0%).
take about 0.3g of this product, weigh it accurately, place it in the top empty bottle, and add the internal standard solution accurately (weigh the appropriate amount of N-propanol, add N ,IV-dimethylformamide is made into a solution containing about 100ug per 1 ml) 3ml to dissolve, seal, as a test solution; In addition, ethanol, acetonitrile and dichloromethane in appropriate amounts are added for precision weighing, A mixed solution containing about 500ug of ethanol, 41ug of acetonitrile and 60ug of dichloromethane per 1 ml was prepared by quantitative dilution with an internal standard solution, and 3ml was accurately weighed, placed in a headspace bottle, sealed, and used as a reference solution. According to the test for determination of residual solvents (General rule 0861, second method), 6% cyanopropylphenyl-94% dimethylpolysiloxane (or similar polar) was used as the stationary liquid; The initial temperature was 35 ° C. For 7 minutes, the temperature was increased to 200°C at a rate of 20°C per minute for 5 minutes; The inlet temperature was 220°C and the detector temperature was 220°C; The equilibrium temperature of the headspace bottle was 80°C, the equilibration time was 20 minutes. Take the reference solution into the headspace, the separation degree of each component peak should meet the requirements. Then the test solution and the reference solution were injected with headspace, and the chromatograms were recorded. According to the internal standard method to calculate the peak area, ethanol, acetonitrile and dichloromethane residues should be in accordance with the provisions.
take this product, at 60°C under reduced pressure drying to constant weight, weight loss should not exceed 0.5% (General rule 0831).
take l.Og of this product and check it according to law (General rule 0841). The retained residue 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 15ml of glacial acetic acid and anhydrous dioxane (take 500ml of dioxane, add 10g of dried 4A molecular sieve, place overnight, get 5ml), slightly temperature to dissolve, add crystal violet indicator liquid 1 drop, with perchloric acid titration solution (0.1 mol/L) titration to a clear blue color of the solution, and the results of the titration were corrected with a blank test. Each 1 ml of perchloric acid titration solution (0.1 mol/L) corresponds to 49.25mg of C20H28N205. C4H404.
angiotensin-converting enzyme inhibitors.
light shielding, sealed storage.
This product contains enalapril maleate (C20H28N2O5 • C4H4O4) should be 90.0% to 110.0% of label.
This product is white or off-white.
with enalapril maleate.
light shielding, sealed storage.
This product contains enalapril maleate (C20H28N2O5 • C4H404) should be 90.0% to 110.0% of the label.
The content of this product is white or white particles or powder.
measured by high performance liquid chromatography (General 0512).
Chromatographic conditions and system applicability test with octanosilane bonded silica as filler, with phosphate buffer solution (0.Olmol / L potassium dihydrogen phosphate solution, adjusted to pH 2.2 with phosphoric acid)-acetonitrile (75:25) as mobile phase; The detection wavelength was 215nm; The column temperature was 50°C. Take appropriate amount of maleic acid, add mobile phase to dissolve and make a solution containing about 0.5mg of maleic acid per 1 ml; Take appropriate amount of impurity I reference, enalapril maleate reference and impurity II reference respectively, the mobile phase was added to dissolve and dilute to prepare a mixed solution containing about 20ug each per 1 ml. 20ul of The maleic acid solution and the mixed solution were injected into the liquid chromatograph, and the chromatograms were recorded. The order of peaks was maleic acid peak, impurity I Peak, enalapril peak and impurity II peak, the tailing factor of enalapril peak should be less than 2.0, the separation degree of maleic acid peak and enalaprilat peak should meet the requirements, and the separation degree between impurity I Peak, enalapril peak and impurity II peak should be greater than 4.0.
Determination of this product 20 capsules, precision weighing, calculate the average loading. Take the contents, mix well, grind finely, weigh an appropriate amount (about 20mg equivalent to enalapril maleate), put it in a 100ml measuring flask, add an appropriate amount of water, shake to dissolve enalapril maleate, dilute it with water to the scale, shake well, filter, take the filtrate as the test solution, take 20 u1 with precision, inject human liquid chromatograph, record the chromatogram; Take an appropriate amount of enalapril maleate reference substance, weigh it with precision, water was added to dissolve and quantitatively diluted to prepare a solution containing about 0.2mg per 1 ml, which was determined by the same method and calculated by the external standard method with the peak area of enalapril.
with enalapril maleate.
(l)5mg (2)10mg
light shielding, sealed storage.