Amlodipine Besylate Tablets

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

Change to read:

Amlodipine Besylate Tablets contain an amount of amlodipine besylate equivalent to (USP 1-May-2021) NLT 90% and NMT 110% of the labeled amount of amlodipine (C₂₀H₂₅ClN₂O₅).

2 IDENTIFICATION

Change to read:

A. The UV spectra of the major peak of the Sample solution correspond to those of the Standard solution, as obtained in the Assay. (USP 1-May-2021)

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

Buffer: Add 7.0 mL of triethylamine into a 1000-mL flask containing 900 mL of water. Adjust the solution with phosphoric acid to a pH of 3.0. (USP 1-May-2021) Dilute with water to volume, and mix well.

Mobile phase: Methanol, acetonitrile, and Buffer (35:15:50)

Standard solution: 0.0275 mg/mL of USP Amlodipine Besylate RS and 0.0025 mg/mL of USP Amlodipine Related Compound A RS in Mobile phase

Sample solution: Nominally 0.02 mg/mL of amlodipine in Mobile phase prepared as follows. Place Tablets (NLT 5) in a suitable volumetric flask, and add a suficient quantity of Mobile phase to disintegrate the Tablets. Shake for 30 min, and dilute with Mobile phase to volume.

Pass the sample through a syringe tip filter of 0.45-μm pore size. Discard the first few milliliters of the filtrate.

3.2 Chromatographic system

Mode: LC

Detector: UV 237 nm. For Identification A, use a diode array detector in the range of 200–400 nm. (USP 1-May-2021)

Column: 3.9-mm × 15-cm; 4- or (USP 1-May-2021) 5-μm packing L1

Flow rate: 1 mL/min

Injection volume: 50 μL

Run time: NLT 3 times the retention time (USP 1-May-2021) of amlodipine

3.3 System suitability

Sample: Standard solution

[Note-The relative retention times for amlodipine related compound A and amlodipine are about 0.5 and 1.0, respectively.]

3.4 Suitability requirements

Resolution: NLT 8.5 between amlodipine related compound A and amlodipine

Tailing factor: NMT 2.0 for amlodipine related compound A and amlodipine

Relative standard deviation: NMT 5.0% for amlodipine related compound A and NMT 2.0% for amlodipine (USP 1-May-2021)

3.5 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of amlodipine (C₂₀H₂₅ClN₂O₅) in the portion of Tablets taken:

Result = (r_u/r_s) × (C_s/C_u)  × (M_r1/M_r2) × 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 = nominal concentration of amlodipine in the Sample solution (mg/mL)

M_r1 = molecular weight of amlodipine, 408.88

M_r2 = molecular weight of amlodipine besylate, 567.05

Acceptance criteria: 90%–110% (USP 1-May-2021)

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

[Note-Do not expose any of the solutions to stainless steel because of the degradation of amlodipine.]

4.1 Test 1

Medium: 0.01 N hydrochloric acid; 500 mL

Apparatus 2: 75 rpm. [Note-Use paddles covered with Teflon or made of any inert material except stainless steel.]

Time: 30 min

Standard solution: (L/360) mg/mL of USP Amlodipine Besylate RS in Medium, where L is the label claim of amlodipine in mg/Tablet. [Note-These solutions are stable for 1 day.] (USP 1-May-2021)

Sample solution: Pass a portion of the solution under test through a suitablefilter of 0.45-μm pore size.

Blank: Medium

Instrumental conditions

Mode: UV

Analytical wavelength: 239 nm

Cell: 1-cm quartz

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of amlodipine (C₂₀H₂₅ClN₂O₅) dissolved:

Result = (A_u/A_s) × C_s× V × (M_r1/M_r2) × (1/L) × 100

A_u = absorbance of amlodipine from the Sample solution

A_s = absorbance of amlodipine from the Standard solution

C_s = concentration of USP Amlodipine Besylate RS (USP 1-May-2021) in the Standard solution (mg/mL)

V = volume of Medium, 500 mL

M_r1 = molecular weight of amlodipine, 408.88

M_r2 = molecular weight of amlodipine besylate, 567.05

L = label claim (mg/Tablet)

Tolerances: NLT 75% (Q) of the labeled amount of amlodipine (C₂₀H₂₅ClN₂O₅) is dissolved.

4.2 Test 2

If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 2.

Medium, Apparatus 2, and Time: Proceed as directed in Test 1.

Buffer A: Dissolve 1.36 g of potassium phosphate, monobasic in 1000 mL of water. Add 5 mL of triethylamine and adjust the solution with phosphoric acid to a pH of 2.0.

Buffer B: Dilute 7.0 mL of triethylamine in 1000 mL of water. Adjust the solution with phosphoric acid to a pH of 3.0.

Mobile phase: Acetonitrile and Buffer A (30:70)

Diluent: Acetonitrile, methanol, and Buffer B (15:35:50)

Standard stock solution: 0.693 mg/mL of USP Amlodipine Besylate RS in Diluent

Standard solution: (L/361) mg/mL of USP Amlodipine Besylate RS in Medium, where L is the label claim of amlodipine in mg/Tablet

Sample solution: Centrifuge a portion of the solution under test for 5 min.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 237 nm

Column: 4.6-mm × 15-cm; 5-μm packing L1

Temperatures

Autosampler: 5°

Column: 35°

Flow rate: 1.5 mL/min

Injection volume: 20 μL

Run time: NLT 1.7 times the retention time of amlodipine

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of amlodipine (C₂₀H₂₅ClN₂O₅) dissolved:

Result = (r_u/r_s)  × C_s × V × (M_r1/M_r2) × (1/L) × 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)

V = volume of Medium, 500 mL

M_r1 = molecular weight of amlodipine, 408.88

M_r2 = molecular weight of amlodipine besylate, 567.05

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of amlodipine (C₂₀H₂₅ClN₂O₅) is dissolved. (USP 1-May-2021)

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Change to read:

5.1 Organic Impurities

Buffer, Mobile phase, Standard solution, and Chromatographic system: Proceed as directed in the Assay.

Sensitivity solution: 0.55 μg/mL of USP Amlodipine Besylate RS in Mobile phase (USP 1-May-2021)

Sample solution: Nominally 0.4 mg/mL of amlodipine in Mobile phase prepared as follows. (USP 1-May-2021) Place a suitable number of

Tablets in a 25-mL volumetric flask.  (USP 1-May-2021) Add about 10 mL of Mobile phase to the flask. Swirl to disintegrate the Tablets, then sonicate for 5 min to completely dissolve, and cool to room temperature. Dilute with Mobile phase to volume. Stir for an additional 15 min using a magnetic stir bar, and pass the sample through a syringe tip filter of 0.45-μm pore size, discarding the first 5 mL.

5.2 System suitability

Samples: Standard solution and Sensitivity solution (USP 1-May-2021)

Suitability requirements: Proceed as directed in the Assayexcept for Signal-to-noise ratio.

Signal-to-noise ratio: NLT 10, Sensitivity solution (USP 1-May-2021)

5.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of amlodipine related compound A (free base) (USP 1-May-2021) in the portion of Tablets taken:

Result = (r_u/r_s) × (C_s/C_u) × (M_r1/M_r2) × 100

r_u = peak response of amlodipine related compound A from the Sample solution

r_s = peak response of amlodipine related compound A from the Standard solution

C_s = concentration of USP Amlodipine Related Compound A RS in the Standard solution (mg/mL)

C_u = nominal concentration of amlodipine in the Sample solution (mg/mL)

M_r1 = molecular weight of amlodipine related compound A (free base), (USP 1-May-2021) 406.86

M_r2 = molecular weight of amlodipine related compound A, 522.94 (USP 1-May-2021)

Calculate the percentage of amlodipine glucose/galactose adduct or amlodipine lactose adduct, if present, and any unspecified degradation product in the portion of Tablets taken:

Result = (r_u/r_s) × (C_s/C_u) × (M_r1/M_r2) × 100

r_u = peak response of amlodipine glucose/galactose adduct, amlodipine lactose adduct, or any unspecified degradation product from the Sample solution

r_s= peak response of amlodipine from the Standard solution

C_s = concentration of USP Amlodipine Besylate RS from the Standard solution (mg/mL)

C_u = nominal concentration of amlodipine in the Sample solution (mg/mL)

M_r1 = molecular weight of amlodipine, 408.88 (USP 1-May-2021)

M_r2 = molecular weight of amlodipine besylate, 567.05

Acceptance criteria: See Table 1.

Table 1

^a This peak is due to the counterion and is not to be reported or included in the total impurities. (USP 1-May-2021)

^b 3-Ethyl 5-methyl [2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-3,5-pyridinedicarboxylate].  (USP 1-May-2021)

^c Formulation-specific impurities.

6 ADDITIONAL REQUIREMENTS

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

Add the following:

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used. (USP 1-May-2021)

Change to read:

USP Reference Standards 〈11〉

USP Amlodipine Besylate RS

USP Amlodipine Related Compound A RS

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

C₂₀H₂₃ClN₂O₅ · C₄H₄O₄   522.94