Metoclopramide Oral Solution

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 Oral Solution contains an amount of metoclopramide hydrochloride (C₁₄H₂₂ClN₃O₂ · HCl · H₂O) equivalent to NLT 90.0% and NMT 110.0% of the labeled amount of metoclopramide (C₁₄H₂₂ClN₃O₂).

2 IDENTIFICATION

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

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

3 ASSAY

Procedure

Mobile phase: Dissolve 2.7 g of sodium acetate in 600 mL of water, and add 400 mL of acetonitrile and 4 mL of tetramethylammonium

hydroxide solution in methanol (25%). Adjust with glacial acetic acid to a pH of 6.5, filter, and degas.

System suitability stock solution: Transfer 125 mg of benzenesulfonamide to a 25-mL volumetric flask. Add 15 mL of methanol, and shake

to dissolve. Dilute with 0.01 M phosphoric acid to volume.

Standard stock solution: 9 mg/mL of USP Metoclopramide Hydrochloride RS in 0.01 M phosphoric acid

System suitability solution: Transfer 15 mL of System suitability stock solution and 5 mL of Standard stock solution into a 250-mL volumetric

flask, and dilute with 0.01 M phosphoric acid to volume.

Standard solution: 180 µg/mL of USP Metoclopramide Hydrochloride RS (equivalent to 160 µg/mL of metoclopramide) from Standard stock

solution. Dilute with 0.01 M phosphoric acid.

Sample solution: Nominally 160 µg/mL of metoclopramide, prepared as follows. Transfer a volume of Oral Solution, equivalent to about 4 mg

of metoclopramide, to a 25-mL volumetric flask, and dilute with 0.01 M phosphoric acid to volume.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 215 nm or diode array. [Note—Use the diode array detector to perform Identification test B.]

Column: 4.6-mm × 25-cm; packing L1

Flow rate: 1.5 mL/min

Injection volume: 20 µL

System suitability

Samples: System suitability solution and Standard solution

Suitability requirements

[Note—The relative retention times for benzenesulfonamide and metoclopramide are 0.2 and 1.0, respectively.]

Resolution: NLT 1.5 between the benzenesulfonamide and metoclopramide peaks, System suitability solution

Tailing factor: NMT 2.0 for the metoclopramide peak, Standard solution

Relative standard deviation: NMT 2.0%, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of metoclopramide (C₁₄H₂₂ClN₃O₂) in the portion of Oral Solution taken:

Result = (r₁ / r₂) × (C₁ / C₂) × (M₁ / M₂) × 100

r₁ = peak response from the Sample solution

r₂ = peak response from the Standard solution

C₁ = concentration from USP Metoclopramide Hydrochloride RS in the Standard solution (µg/mL)

C₂ = nominal concentration of metoclopramide in the Sample solution (µg/mL)

M₁ = molecular weight of metoclopramide, 299.80

M₂ = molecular weight of anhydrous metoclopramide hydrochloride, 336.26

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

Uniformity of Dosage Units 〈905〉

For oral solution packaged in single-unit containers: Meets the requirements

Deliverable Volume 〈698〉

For oral solution packaged in multiple-unit containers: Meets the requirements

5 IMPURITIES

Organic Impurities

Mobile phase: Prepare a 1.88 g/L solution of sodium 1-hexanesulfonate solution (0.01 M solution) in a mixture of acetonitrile and water

(60:40), and adjust with glacial acetic acid to a pH of 4.0.

Standard solution: 5.5 µg/mL of USP Metoclopramide Hydrochloride RS in Mobile phase

Sample solution: Dilute a volume of Oral Solution with Mobile phase to obtain a solution containing about 1.0 mg/mL of metoclopramide.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 265 nm

Column: 4.6-mm × 25-cm; 5-µm packing L1

Flow rate: 2 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 1.8

Relative standard deviation: NMT 5.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any individual impurity in the portion of Oral Solution taken:

Result = (r₁ / r₂) × (C₁ / C₂) × (M₁ / M₂) × 100

r₁ = peak response of each 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 (µg/mL)

C₂ = nominal concentration of metoclopramide in the Sample solution (µg/mL)

M₁ = molecular weight of metoclopramide, 299.80

M₂ = molecular weight of anhydrous metoclopramide hydrochloride, 336.26

Acceptance criteria: NMT 0.5% of any individual impurity is found. Disregard any peak with a relative retention time of 0.5 or less.

6 SPECIFIC TESTS

pH 〈791〉: 2.0–5.5

7 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight, light-resistant containers, and store at controlled room temperature. Protect from freezing.

USP Reference Standards 〈11〉

USP Metoclopramide Hydrochloride RS