Carbidopa

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

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

DOWNLOAD PDF HERE

C₁₀H₁₄N₂O₄ · H₂O 244.24

C₁₀H₁₄N₂O₄ 226.23

Benzenepropanoic acid, α-hydrazino-3,4-dihydroxy-α-methyl-, monohydrate, (S)-;

(−)-l-α-Hydrazino-3,4-dihydroxy-α-methylhydrocinnamic acid monohydrate CAS RN®: 38821-49-7; UNII: MNX7R8C5VO.

Anhydrous CAS RN®: 28860-95-9; UNII: KR87B45RGH.

1 DEFINITION

Carbidopa contains NLT 98.0% and NMT 102.0% of carbidopa (C₁₀H₁₄N₂O₄ · H₂O).

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197M (CN 1-May-2020)

B. The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

Procedure

Buffer: 0.05 M monobasic sodium phosphate, adjusted with phosphoric acid to a pH of 2.7

Mobile phase: Alcohol and Buffer (5:95)

System suitability solution: 0.1 mg/mL of USP Carbidopa RS and 0.1 mg/mL of USP Methyldopa RS in Mobile phase

Standard solution: 0.5 mg/mL of USP Carbidopa RS in Mobile phase. [Note—Use gentle heat and ultrasonification, if necessary, to dissolve.]

Sample solution: 0.5 mg/mL of Carbidopa in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 3.9-mm × 30-cm; packing L1

Flow rate: 1 mL/min

Injection volume: 20 μL

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for methyldopa and carbidopa are about 0.8 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 0.9 between methyldopa and carbidopa, System suitability solution

Relative standard deviation: NMT 1.5%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the concentration, in mg/mL, of carbidopa (C₁₀H₁₄N₂O₄ · H₂O) in the Standard solution (C_S):

Result = C_S2 × (M_r1/M_r2)

C_S2 = concentration of USP Carbidopa RS, as determined using the value on the USP Reference Standard label, in the Standard solution (mg/mL)

M_r1 = molecular weight of carbidopa monohydrate, 244.24

M_r2 = molecular weight of anhydrous carbidopa, 226.23

Calculate the percentage of carbidopa (C₁₀H₁₄N₂O₄ · H₂O) in the portion of Carbidopa taken:

Result = (r_U/r_S) x (C_S/C_U ) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

C_S = concentration of carbidopa (C₁₀H₁₄N₂O₄ · H₂O) in the Standard solution (mg/mL)

C_U = concentration of Carbidopa in the Sample solution (mg/mL)

Acceptance criteria: 98.0%–102.0%

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Limit of Methyldopa and Carbidopa Related Compound A

Mobile phase, System suitability solution, Standard solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Impurity standard solution: 2.5 μg/mL of USP Methyldopa RS and 2.5 μg/mL of USP Carbidopa RS in Mobile phase

Analysis

Samples: Sample solution and Impurity standard solution

[Note—The relative retention times for methyldopa, carbidopa, and carbidopa related compound A are about 0.8, 1.0, and 1.8, respectively.]

Calculate the percentage of methyldopa in the portion of Carbidopa taken:

Result = (r_U/r_S) x (C_S/C_U ) × 100

r_U = peak response of methyldopa from the Sample solution

r_S = peak response of methyldopa from the Impurity standard solution

C_S = concentration of USP Methyldopa RS in the Impurity standard solution (μg/mL)

C_U = concentration of the Sample solution (μg/mL)

Calculate the percentage of carbidopa related compound A in the portion of Carbidopa taken:

Result = (r_U/r_S) x (C_S/C_U ) × 100

r_U = peak response of carbidopa related compound A from the Sample solution

r_S = peak response of carbidopa from the Impurity standard solution

C_S = concentration of USP Carbidopa RS in the Impurity standard solution (μg/mL)

C_U = concentration of the Sample solution (μg/mL)

Acceptance criteria: NMT 0.5% of methyldopa and NMT 0.5% of carbidopa related compound A

5 SPECIFIC TESTS

Optical Rotation, Specific Rotation〈781S〉

Sample solution: 10 mg/mL in 0.7 g/mL of aluminum chloride solution (prepared using the hexahydrate form of the aluminum salt) that has been filtered and adjusted with 0.25 N sodium hydroxide to a pH of 1.5

Acceptance criteria: −21.0° to −23.5° calculated as the monohydrate

Loss on Drying 〈731〉

Analysis: Heat 1 g in a suitable vacuum drying apparatus at 100° and a pressure of NMT 5 mm of mercury to constant weight. Cool, and weigh.

Acceptance criteria: 6.9%–7.9%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed, light-resistant containers.

USP Reference Standards 〈11〉

USP Carbidopa RS

USP Methyldopa RS