Enalaprilat Injection

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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Enalaprilat Injection is a sterile solution of enalaprilat in a suitable vehicle for injection. It contains not less than 90.0 percent and not more than 110.0 percent of the labeled amount of enalaprilat (C₁₈H₂₄N₂O₅)

Packaging and storage—Preserve in single dose or in multiple-dose containers, and store at controlled room temperature.

Identification—

A: The retention time of the enalaprilat peak in the chromatogram of the Assay preparation corresponds to that of the corresponding peak in the chromatogram of the Standard preparation, obtained as directed in the Assay.

BACTERIAL ENDOTORING TEST (85)-It contains no more than 280 USP Endotoxin Units per mg of enalaprilat.

STERILITY TESTA (71): meets the requirements.

PH(791); between 6.5 and 7.5.

PARTICULATE MATTER IN INJECTIONS (7BB): meets the requirements for small-volume injections.

Change to read:

OSMOLALITY AND OSMOLARITY (785)

Osmolality between 276 to 305 mOsm per kg.

Related compounds—

Diluent-Prepare a mixture of water and acetonitrile (84:16).

Buffer solution-Dilute 3.4 mL of phosphoric acid with water to 1 L. Adjust with potassium hydroxide to a pH of 2.5.

Solution A-Use a mixture of Buffer solution and acetonitrile (84:16).

Solution 8-Use acetonitrile.

Mobile phase-Use variable mixtures of Solution A and Solution B. Make adjustments if necessary (see System Suitability under

Chromatography (621)).

Stock solution A-Dissolve 20 mg of USP Enalaprilat RS in a 100 ml volumetric flask with approximately 80 ml. of Diluent. Heat at 80° for 24 hours to generate enalaprilat related compound A. Cool the solution to room temperature, and dilute with Diluent to volume.

Stock solution B-Dissolve 10 mg of USP Enalapril Maleate RS in a 200-ml, volumetric flask, and dilute with Diluent to volume.

Stock solution C-Dissolve accurately weighed quantities of benzyl alcohol, benzaldehyde, and benzoic acid in Diluent. Dilute quantitatively. and stepwise if necessary, with Diluent to obtain a solution having a known concentration of 0.1 mg per mL of each of the three substances.

System suitability solution-Pipet 4.0 mL of Stock solution A, 5 mL of Stock solution 8, and 5 mL of Stock solution C into a 25-ml volumetric flask, and dilute with Diluent to volume to obtain a solution containing about 0.0032 mg per mL of enalaprilat related impurity A, 0.01 mg per mL of enalapril, and 0.02 mg per ml of each of benzyl alcohol, benzaldehyde, and benzoic acid, respectively.

Test solution-Transfer an accurately measured volume of Injection, equivalent to about 12.5 mg of enalaprilat, to a 25 mL volumetric flask.

Dilute with Diluent to volume, and mix.

Diluted test solution-Dilute the Test solution (1 in 100) with Diluent to obtain a solution having a known concentration of 0.005 mg per ml. (corresponds to 1% of the Test solution).

Chromatographic system (see COMATOGRAPHY (621))-The chromatograph is equipped with 215-nm detector and a 4a 4.6-mm × 15-cm, 5-μm column that contains packing L1. The column temperature is maintained at 60°. The flow rate is about 1.5 ml. per minute. The chromatograph is programmed as follows:

Chromatograph the System sutabilty solution and the Diluted rest solution, and record the peak responses as directed for Proceduw the resolution, R between enalapril maleute and enalaprilat stated impurity A is not less than 1:2, the capacity factor for enalaprikat met les than 1.5 and the relative standard deviation of the enalapriliat peak in replicate injections of the Diluted test solution is not more than 2.01%. Procedure-Separately inject equal volumes (about 20 pl) of the Diluted test solution and the Teat solution into the chromatograph, record the chromatogram, and measure the peak response for enalaprillat in the Diluted test solution and all of the peak responses from the Test solution that do not comespond to enalaprilat, benzyl alcohol, benzoic acid, benzaldehyde, and benzyl alcohol related compounds (see Table 1 for RRT). Calculate the percentage of specified and unspecified impurities using the formula:

(r_i/r_s)

in which r_i is the peak response for each specified impurity in the Test solution and r_s is the peak response for enalaprilat in the Diluted test solution the impurities meet the specified limits in Table 1.

Benzyl alcohol content (present)—

Buffer solution Mobile phase, System suitability solution, and Chromatographic spalem-Proceed as directed in the Assa

Standard solution-Dissolve an accurately weighed quantity of USP Benzyl Alcohol in Mobile phase to obtain a solution having a known concentration of 12.72 mg per mL

Test solution-Use the Assay preparation, prepared as directed in the Assay.

Procedure-Proceed as directed in the Assay. Calculate the percentage of benzyl alcohol, based on the label claim, in the volume of injection taken by the formula:

1000(C_S /C_U)(r_U/(r_S) 

in which C_s, Is the concentration, in mg per mL, of SIP Bent Akahul RS in the Standard solution, C_u is the concentration, in mig por ml, of benzyl alcohol in the Test anlution, andr andr, are the benzyl alcohol peak responses obtained from the fest solution and the Standard solution, respectively, between 75.0% and 120.0% of the labeled amount is found

Other requirements—It meets the requirements under stions and implanted Drum Products (1)

Assay—

Buffer solution-Prepare a solution of 0.05 M monobasic potassium phosphate. Adjust with phosphoric acid to a pH of 2.5

Mobile phase Prepare a filtered and degassed mixture of Buffer solution and acetonitrile (84: 16) Make adjustments if necessary (see

System Suitability under Chromatograhy (621)

System sutability preparation Use the Standard preparation

Standard preparation-Dissolve an accunstely weighed quantity of 100P Enalaprilat RS and USP Benzyl Alcohol RS in Bulle aslution, and dilute quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known.concentration of about 6.1 mg per me of enalaprilar and 0.72 mg per ml. of benzyl alcohal

Assay preparation-Transfer an accurately measured volume of injection, equivalent to about 5 mg of enalaprilat, to a 50 m volumetric flask Dilute with Mibile phase to volume, and mix

Chromatographic cудет (see 62133-The liquid chromatograph is equipped with a 215-nm and 258-mm detector (use 215 nem as the initial wavelength, and switch to 258 em after the slution of enalaprilat and before the elution of benzyl alcohol) and a 46 mm 15 om, 5-um column that contains packing 11. The flow rate is about 1.5 mi par minuta. The column temperature is maintained at 60 Chromatograph the System suitability preparation, and record the peak responses as directed for Procedure the resolution, Fe between benzyl alcohol and enalaprilat is not less than 3.0, the tailing factor for benzyl alcohol and the enalapitiat peaks is not more than 1.5, and the native standard deviation for replicate injections is not more than 2.0

Procedure-Separately inject equal volumes (about 20 ut) of the Standard prepanation and the Assay preparation into the chromatograph record the chromatograms, and measure all of the peak responses. Calculate the quantity, in percentage of the label claim of enalaprilat (CHNO) in the portion of Injection taken by the formula

1000(C_S /C_U)(r_U/(r_S) 

in which C_s is the concentration, in mg per ml, of USP Enalariat RS in the Standard preparation C_u is the concentration, in mg per ml, of onalaprilat in the Assay preparation, based on the label claim; and r_u and r_s, are the peak responses obtained from the Assay preparation and the Standard preparation, respectively