Nimodipine

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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C₂₁H₂₆N₂O₇         418.44

3,5-Pyridinedicarboxylic acid, 1,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-, 2-methoxyethyl 1-methylethyl ester;

Isopropyl 2-methoxyethyl 1,4-dihydro-2,6-dimethyl-4-(m-nitrophenyl)-3,5-pyridinedicarboxylate CAS RN^®: 66085-59-4; UNII: 57WA9QZ5WH.

1 DEFINITION

Nimodipine contains NLT 98.0% and NMT 102.0% of nimodipine (C₂₁H₂₆N₂O₇), calculated on the dried basis.

[NOTE-Throughout the following procedures, protect samples, the Reference Standards, and solutions containing them by conducting the procedures without delay, under subdued light, or using low-actinic glassware.]

2 IDENTIFICATION

Change to read:

A. ^▲SPECTROSCOPIC IDENTIFICATION TESTS (197), Infrared Spectroscopy: 197K _{▲(CN 1-MAY-2020)}

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

3 ASSAY

PROCEDURE

Mobile phase: Methanol, tetrahydrofuran, and water (20:20:60)

Standard solution: 0.3 mg/mL of USP Nimodipine RS prepared as follows. Transfer a quantity of USP Nimodipine RS to a suitable volumetric flask, dissolve in a volume of tetrahydrofuran equivalent to 10% of the total volume, and dilute with Mobile phase to volume.

Sample solution: 0.3 mg/mL of Nimodipine prepared as follows. Transfer a quantity of Nimodipine to a suitable volumetric flask, dissolve in a volume of tetrahydrofuran equivalent to 10% of the total volume, and dilute with Mobile phase to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 235 nm

Column: 4.6-mm x 12.5-cm; 5-µm packing L1

Column temperature: 40°

Flow rate: 2 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 0.73%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of nimodipine (C₂₁H₂₆N₂O₇) in the portion of Nimodipine taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of nimodipine from the Sample solution

r_S = peak response of nimodipine from the Standard solution

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

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

Acceptance criteria: 98.0%-102.0% on the dried basis

4 IMPURITIES

4.1 RESIDUE ON IGNITION (281)

NMT 0.1%

4.2 ORGANIC IMPURITIES

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

Standard stock solution A: 1.6 mg/mL of USP Nimodipine RS prepared as follows. Transfer a quantity of USP Nimodipine RS to a suitable volumetric flask, dissolve in a volume of tetrahydrofuran equivalent to 10% of the total volume, and dilute with Mobile phase to volume.

Standard stock solution B: 0.8 mg/mL each of USP Nimodipine RS and USP Nimodipine Related Compound A RS prepared as follows. Transfer quantities of USP Nimodipine RS and USP Nimodipine Related Compound A RS to a suitable volumetric flask, dissolve in a volume of tetrahydrofuran equivalent to 10% of the total volume, and dilute with Mobile phase to volume.

Standard solution A: 3.2 µg/mL of USP Nimodipine RS from Standard stock solution A in Mobile phase

Standard solution B: 1.6 µg/mL each of USP Nimodipine RS and USP Nimodipine Related Compound A.RS from Standard stock solution B in

Mobile phase

Sample solution: 1.6 mg/mL of Nimodipine prepared as follows. Dissolve 40 mg of Nimodipine in 2.5 mL of tetrahydrofuran, and dilute with Mobile phase to 25 mL.

System suitability

Sample: Standard solution B

[NOTE-The relative retention times for nimodipine related compound A and nimodipine are about 0.9 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 1.5 between nimodipine related compound A and nimodipine

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution A, Standard solution B, and Sample solution

Calculate the percentage of nimodipine related compound A in the portion of Nimodipine taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

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

r_S = peak response of nimodipine related compound A from Standard solution B

C_S = concentration of USP Nimodipine Related Compound A RS in Standard solution B (µg/mL)

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

Calculate the percentage of any other impurity in the portion of Nimodipine taken:

                         Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of nimodipine from Standard solution A

C_S = concentration of USP Nimodipine RS in Standard solution A (µg/mL)

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

Acceptance criteria

Nimodipine related compound A: NMT 0.1%

Any unspecified impurity: NMT 0.2%

Total impurities: NMT 0.5%

5 SPECIFIC TESTS

5.1 OPTICAL ROTATION (781S), Procedures. Specific Rotation

Sample solution: 50 mg/mL in acetone

Acceptance criteria: -0.10° to +0.10°, at 20°

5.2 LOSS ON DRYING (731)

Analysis: Dry at 105° for 4 h.

Acceptance criteria: NMT 0.5%

6 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight, light-resistant containers, and store at controlled room temperature.

USP REFERENCE STANDARDS (11)

USP Nimodipine RS

USP Nimodipine Related Compound A RS

2-Methoxyethyl-1-methylethyl-2,6-dimethyl-4-(3-nitrophenyl)pyridine-3,5-dicarboxylate.

C₂₁H₂₄N₂O₇           416.42