Captopril Tablets

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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1 DEFINITION

Captopril Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of captopril (C₉H₁₅NO₃S).

2 IDENTIFICATION

Delete the following:

A. THIN-LAYER CHROMATOGRAPHIC IDENTIFICATION TEST (201)

Standard solution: 4 mg/mL in methanol

Sample solution: 4 mg/mL of captopril in methanol prepared as follows. Dissolve the equivalent to 100 mg of captopril from a portion of powdered Tablets, taken in a conical flask, in 25 mL of methanol. Stir for 30 min using a magnetic stirrer, and centrifuge. Use the clear supernatant.

Chromatographic system

Application volume: 50 µL as streaks

Developing solvent system: Toluene, methanol, and glacial acetic acid (75:1:25)

Spray reagent: Freshly prepared mixture of 1 volume of ammonium hydroxide and 6 volumes of a solution of 0.04% 5,5'-dithiobis(2-nitrobenzoic acid) in methanol

Analysis: Proceed as directed in the chapter. Locate the spots on the plate by lightly spraying with Spray reagent.

Acceptance criteria: Meet the requirements 2S (USP41)

Add the following:

. A. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay-25 (USP41)

Add the following:

B. The UV spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay 2S (USP41)

3 ASSAY

Change to read:

PROCEDURE

Protect solutions from exposure to air and use within 8 h of preparation.

Mobile phase: 550 mL of methanol and 450 mL of water containing 0.50 mL of phosphoric acid

Standard solution: 1 mg/mL of USP Captopril RS and 0.05 mg/mL of USP Captopril Disulfide RS in Mobile phase

Sample solution: Nominally equivalent to 1 mg/mL of captopril prepared as follows. Transfer NLT 20 Tablets into a suitable volumetric flask and add Mobile phase to fill about 50% of the volume of the flask. Sonicate for 15 min. Dilute with Mobile phase to volume, shake by mechanical means for 15 min, and filter.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 220 nm. For Identification B, use a diode array detector in the range of 190-400 nm. 2S (USP41)

Column: 4.6-mm x 25-cm; 5-pm 2S (USP41) packing L12S (USP41)

Flow rate: 1 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

[NOTE-The relative retention times for captopril and captopril disulfide are 0.5 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between captopril and captopril disulfide

Relative standard deviation: NMT 2.0% for both the captopril and captopril disulfide peaks 25 (USP41)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of captopril (C₉H₁₅NO₃S) in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U  = peak response of captopril from the Sample solution

r_s = peak response of captopril from the Standard solution

C_S = concentration of USP Captopril RS in the Standard solution (mg/mL)

C_u = nominal concentration of captopril in the Sample solution (mg/mL)

Acceptance criteria: 90.0%~110.0%

4 PERFORMANCE TESTS

Change to read:

DISSOLUTION (711) [NOTE-Completely deaerate the Medium to minimize exposure of captopril to air, and analyze the samples immediately.]

Medium: 0.01 N bydrochloric acid: 900 mL

Apparatus 1: 50 rpm

Time: 20 min

Standard solution: USP Captopril RS at a known concentration in Medium

Sample solution: Pass a portion of the solution under test through a suitable filter. Dilute with Medium, if necessary, to a concentration similar to that of the Standard solution.

Instrumental conditions

Mode: UV

Analytical wavelength: 205 nm

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of captopril (C₉H₁₅NO₃S) dissolved:

Result = (A/A)x(C/L)xVxDx100

A_u = absorbance of the Sample solution

As= absorbance of the Standard solution

C_s = concentration of USP Captopril RS in the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL

D = dilution factor for the Sample solution 25 (USP41)

Tolerances: NLT 80% (Q) of the labeled amount of captopril (C₉H₁₅NO₃S) is dissolved.

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 IMPURITIES

LIMIT OF CAPTOPRIL DISULFIDE

Protect solutions from exposure to air and use within 8 h of preparation.

Mobile phase and Chromatographic system: Proceed as directed in the Assay.

System suitability solution: Use the Standard solution prepared as directed in the Assay.

Standard solution: 0.05 mg/ml of USP Captopril Disulfide RS in Mobile phase

Sample solution: Nominally 1 mg/ml of captopril in Mobile phase prepared as follows. Transfer 25 mg of captopril from NLT 20 finely powdered Tablets into a suitable centrifuge tube. Add 25 mL of Mobile phase, sonicate for 15 min, and centrifuge. Use the clear supernatant.

System suitability

Samples: System suitability solution and Standard solution [NOTE-The relative retention times for captopril and captopril disulfide are 0.5 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 2.0 between captopril and captopril disulfide, System suitability solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of captopril disul

de in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) × 100

r_U = peak response of captopril disulfide from the Sample solution

r_S = peak response of captopril disulfide from the Standard solution

C_s = concentration of USP Captopril Disulfide RS in the Standard solution (mg/mL)

C_u = nominal concentration of captopril in the Sample solution (mg/mL)

Acceptance criteria: NMT 3.0%

6 ADDITIONAL REQUIREMENTS

Change to read:

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.2S (USP41)

Change to read:

USP Reference Standards 〈11〉

USP Captopril RS

USP Captopril Disulfide RS

(2′S)-[(2S,2′S)-3,3′-Disulfanediylbis(2-methylpropanoyl)]di-l-proline.2S (USP41)

C₁₈H₂₈N₂O₆S₂ 432.55