Amlodipine Besylate

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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C₂₀H₂₅ClN₂O₅ · C₆H₆O₃S  567.05

3,5-Pyridinedicarboxylic acid, 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-1,4-dihydro-6-methyl-, 3-ethyl 5-methyl ester, (±)-,monobenzenesulfonate;

3-Ethyl 5-methyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate benzenesulfonate (USP 1-Aug-2023) CAS RN®: 111470-99-6; UNII: 864V2Q084H.

Monohydrate

C₂₀H₂₅ClN₂O₅ · C₆H₆O₃S · H₂O (USP 1-Aug-2023) 585.07 CAS RN®: 532929-67-2; UNII: V912825CB9. (USP 1-Aug-2023)

1 DEFINITION

Amlodipine Besylate is anhydrous or hydrated and contains NLT 97.0% and NMT 102.0% of amlodipine besylate (C₂₀H₂₅ClN₂O₅ · C₆H₆O₃S), calculated on the anhydrous basis.

2 IDENTIFICATION

Change to read:

A. Spectroscopic Identification Tests 〈197〉, Infrared Spectroscopy: 197A or (USP 1-Aug-2023) 197M

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

Change to read:

3.1 Procedure

[Note-Protect the solutions containing amlodipine besylate from light.]

Solution A: 1.36 g/L of potassium phosphate, monobasic in water prepared as follows. Dissolve 1.36 g of potassium phosphate, monobasic with 950 mL of water. Adjust with phosphoric acid to a pH of 2.5 ± 0.1. Dilute with water to 1 L.

Solution B: Methanol

Mobile phase: See Table 1.

Table 1

Diluent: Methanol and water (50:50)

Standard solution: 0.5 mg/mL of USP Amlodipine Besylate RS in Diluent

Sample solution: 0.5 mg/mL of Amlodipine Besylate in Diluent

3.2 Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 240 nm

Column: 2.1-mm × 5-cm; 1.7-μm packing L1

Column temperature: 40°

Flow rate: 0.5 mL/min

Injection volume: 2 μL

3.3 System suitability

Sample: Standard solution

3.4 Suitability requirements

Tailing factor: NMT 2.5

Relative standard deviation: NMT 0.73% (USP 1-Aug-2023)

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of amlodipine besylate (C₂₀H₂₅ClN₂O₅ · C₆H₆O₃S) in the portion of Amlodipine Besylate taken:

Result = (r_U/r_S) × (C_S/C_U)× 100

r_U = peak response of amlodipine from the Sample solution

r_S = peak response of amlodipine from the Standard solution

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

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

Acceptance criteria: 97.0%–102.0% on the anhydrous basis

4 IMPURITIES

Residue on Ignition 〈281〉: NMT 0.2%

Change to read:

4.1 Organic Impurities

Solution A, Solution B, Mobile phase, Diluent, Sample solution, and Chromatographic system: Proceed as directed in the Assay.

[Note-Protect the solutions containing amlodipine besylate and amlodipine related compounds from light.]

Impurity stock solution: 0.1 mg/mL of USP Amlodipine Related Compound F RS in Diluent. Sonicate to dissolve.

System suitability solution: 0.5 mg/mL of USP Amlodipine Besylate RS and 1.5 μg/mL of USP Amlodipine Related Compound F RS in Diluent prepared as follows. Transfer an appropriate quantity of USP Amlodipine Besylate RS to a suitable volumetric flask. Add an appropriate volume of the Impurity stock solution to the flask. Dilute with Diluent to volume.

Sensitivity solution: 0.25 μg/mL of USP Amlodipine Besylate RS in Diluent

Standard solution: 0.5 μg/mL of USP Amlodipine Besylate RS in Diluent

4.2 System suitability

Samples: System suitability solution, Sensitivity solution, and Standard solution

[Note-See Table 2 for the relative retention times.]

4.3 Suitability requirements

Resolution: NLT 3.0 between amlodipine related compound F and amlodipine, System suitability solution

Tailing factor: NMT 2.5 for amlodipine, System suitability solution

Relative standard deviation: NMT 5.0%, Standard solution

Signal-to-noise ratio: NLT 10, Sensitivity solution

4.4 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of any specified and unspecified impurity in the portion of Amlodipine Besylate taken:

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × 100

r_U = peak response of each impurity from the Sample solution

r_S = peak response of amlodipine from the Standard solution

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

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

F = relative response factor (see Table 2)

Acceptance criteria: See Table 2. The reporting threshold is 0.05%.

Table 2

^a This peak is due to the counterion and is not to be reported or included in the total impurities.

^b 3-Ethyl 5-methyl [2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-3,5-pyridinedicarboxylate].

^c Diethyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate.

^d 3-Ethyl 5-methyl 4-(2-chlorophenyl)-2-{[2-(2-[(2-hydroxyethyl)carbamoyl]benzamido)ethoxy]methyl}-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate.

^e 3-Ethyl 5-methyl 4-(2-chlorophenyl)-2-{[2-(1,3-dioxoisoindolin-2-yl)ethoxy]methyl}-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate. (USP 1-Aug-2023)

5 SPECIFIC TESTS

Optical Rotation 〈781A〉, Procedures, Angular Rotation

Sample solution: 10 mg/mL of Amlodipine Besylate in methanol

Acceptance criteria: −0.10° to +0.10°, measured at 20°

Water Determination 〈921〉, Method I: NMT 0.5% for the anhydrous form. If labeled as the hydrated form, the limit is 3.1%–5.0%.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers, protected from light. Store at room temperature.

Labeling: Where it is the hydrated form, the label so indicates.

Change to read:

USP Reference Standards 〈11〉

USP Amlodipine Besylate RS

USP Amlodipine Related Compound F RS

Dimethyl 2-[(2-aminoethoxy)methyl]-4-(2-chlorophenyl)-6-methyl-1,4-dihydropyridine-3,5-dicarboxylate maleate.

C₁₉H₂₃ClN₂O₅ · C₄H₄O₄  510.92