Metoclopramide Injection

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

1 DEFINITION

Metoclopramide Injection is a sterile solution of Metoclopramide Hydrochloride in Water for Injection. It contains the equivalent of 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 500 mL of water. Add 500 mL of acetonitrile and 2 mL of tetramethylammonium hydroxide

solution in methanol (1 in 5), and mix. Adjust with glacial acetic acid to a pH of 6.5, filter, and degas.

System suitability stock solution: Transfer 12.5 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: 0.9 mg/mL of USP Metoclopramide Hydrochloride RS in 0.01 M phosphoric acid

System suitability solution: Transfer 5 mL of System suitability stock solution and 5 mL of Standard stock solution into a 100-mL volumetric

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

Standard solution: 45 µg/mL of USP Metoclopramide Hydrochloride RS (equivalent to 40 µg/mL of metoclopramide) from Standard stock

solution. Dilute with 0.01 M phosphoric acid.

Sample solution: Nominally 40 µg/mL of metoclopramide, prepared as follows. Transfer a volume of Injection, equivalent to about 40 mg of

metoclopramide, to a 100-mL volumetric flask, and dilute with 0.01 M phosphoric acid to volume. Transfer 10.0 mL of this solution to a 100-

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 0.7 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 Injection 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 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: 90.0%–110.0%

4 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 Injection 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 Injection 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.

5 SPECIFIC TESTS

pH 〈791〉: 2.5–6.5

Bacterial Endotoxins Test 〈85〉: NMT 2.5 USP Endotoxin Units/mg of metoclopramide

Particulate Matter in Injections 〈788〉: It meets the requirements for small-volume injections.

Other Requirements: It meets the requirements in Injections and Implanted Drug Products 〈1〉.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in single-dose or multiple-dose containers, preferably of Type I glass, protected from light.

[Note—Injection containing an antioxidant agent does not require protection from light.] Store at controlled room temperature.

USP Reference Standards 〈11〉

USP Metoclopramide Hydrochloride RS