Metoclopramide Hydrochloride

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

Metoclopramide Hydrochloride contains NLT 98.0% and NMT 101.0% of metoclopramide hydrochloride

(C₁₄H₂₂ClN₃O₂ · HCl), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

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

B. Identification Tests—General, Chloride 〈191〉

Sample solution: Dissolve 100 mg in 2 mL of water, and acidify the solution with dilute nitric acid.

Acceptance criteria: Meets the requirements

3 ASSAY

Procedure

Sample: 250 mg

Analysis: Dissolve the Sample in a mixture of 5.0 mL of 0.01 N hydrochloric acid and 50 mL of alcohol.

Titrate with 0.1 N sodium hydroxide VS (see Titrimetry 〈541〉), determining the endpoint potentiometrically.

Read the volume of 0.1 N sodium hydroxide added between the two points of inflection.

Each mL of 0.1 N sodium hydroxide is equivalent to 33.63 mg of the anhydrous metoclopramide hydrochloride

(C₁₄H₂₂ClN₃O₂ · HCl).

Acceptance criteria: 98.0%–101.0% on the anhydrous basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.1%

Organic Impurities

Buffer: Dissolve 6.8 g of monobasic potassium phosphate in 700 mL of water.

Add 0.2 mL of N,N-dimethyloctylamine, and adjust with dilute phosphoric acid to a pH of 4.0.

Dilute with water to 1000 mL.

Mobile phase: Acetonitrile and Buffer (250:1000)

Standard stock solution: 0.1 mg/mL each of USP Metoclopramide Hydrochloride RS,

USP Metoclopramide Related Compound A RS,

USP Metoclopramide Related Compound B RS, and

USP Metoclopramide Related Compound D RS in Mobile phase

Standard solution: 2.0 µg/mL each of USP Metoclopramide Hydrochloride RS,

USP Metoclopramide Related Compound A RS,

USP Metoclopramide Related Compound B RS, and

USP Metoclopramide Related Compound D RS in Mobile phase from the Standard stock solution

Sample solution: 1.0 mg/mL of Metoclopramide Hydrochloride in Mobile phase

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 4.6-mm × 25-cm; 5-µm packing L7

Flow rate: 1.5 mL/min

Injection volume: 10 µL

Run time: At least 8 times the retention time of the metoclopramide peak

System suitability

Sample: Standard solution

Suitability requirements

Resolution: NLT 3.0 for metoclopramide related compound A and metoclopramide

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each of metoclopramide related compounds A, B, and D in the portion of

Metoclopramide Hydrochloride taken:

Result = (r₁ / r₂) × (C₁ / C₂) × 100

r₁ = peak response of the relevant metoclopramide related compound from the Sample solution

r₂ = peak response of the relevant metoclopramide related compound from the Standard solution

C₁ = concentration of the relevant USP Metoclopramide Related Compound RS in the Standard solution (mg/mL)

C₂ = concentration of Metoclopramide Hydrochloride in the Sample solution (mg/mL)

Calculate the percentage of any other individual impurity in the portion of Metoclopramide Hydrochloride taken:

Result = (r₁ / r₂) × (C₁ / C₂) × 100

r₁ = peak response of any other individual impurity from the Sample solution

r₂ = peak response of metoclopramide from the Standard solution

C₁ = concentration of USP Metoclopramide Hydrochloride RS in the Standard solution (mg/mL)

C₂ = concentration of Metoclopramide Hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: See Table 1.

Table 1

ᵃ 4-Acetamido-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide.

ᵇ Methyl 4-acetamido-5-chloro-2-methoxybenzoate.

5 SPECIFIC TESTS

Water Determination, Method I 〈921〉: 4.5%–6.0%

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers. Store at room temperature.

USP Reference Standards 〈11〉

USP Metoclopramide Hydrochloride RS

USP Metoclopramide Related Compound A RS

N-Acetylmetoclopramide.

4-Acetamido-5-chloro-N-[2-(diethylamino)ethyl]-2-methoxybenzamide.

C₁₄H₂₁ClN₃O₂ 341.83

USP Metoclopramide Related Compound B RS

N-Acetyl methyl ester analog.

Methyl 4-acetamido-5-chloro-2-methoxybenzoate.

C₁₁H₁₂ClNO₄ 257.67

USP Metoclopramide Related Compound D RS

Methyl 4-acetamido-2-methoxybenzoate.

C₁₀H₁₁NO₄ 223.23