Telmisartan and Amlodipine 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

Telmisartan and Amlodipine Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount each of telmisartan and amlodipine.

2 IDENTIFICATION

A. The retention times of the two major peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.

B. The UV spectra of the two major peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay.

3 ASSAY

Change to read:

Procedure

Buffer: 0.022 M monobasic sodium phosphate dihydrate and 2 mL of triethylamine in 1 L of water. Adjust with phosphoric acid to a pH of 6.0.

Mobile phase: Acetonitrile and Buffer (40:60)

Diluent: Add 5 mL of triethylamine to 500 mL of water. Add 500 mL of acetonitrile and mix.

Standard stock solution 1: 0.4 mg/mL of USP Telmisartan RS in Diluent

Standard stock solution 2: 0.4 mg/mL of USP Amlodipine Besylate RS in Diluent

Standard solution: Prepare the following solutions of USP Telmisartan RS and USP Amlodipine Besylate RS in Diluent at the concentrations shown in Table 1. Transfer a suitable volume of Standard stock solution 1 and Standard stock solution 2 into a suitable volumetric flask.

Dilute with Diluent to volume.

Table 1

Sample solution: Transfer Tablets (NLT 10) to a suitable volumetric flask. Add acetonitrile to about 20% of the volume of the flask, and sonicate for 5 min with intermittent shaking. Add Diluent to about 80% of the flask volume and sonicate until the Tablets are completely dispersed. Dilute with Diluent to volume. Centrifuge and use the supernatant. Dilute with Diluent, if necessary, to obtain the solutions of nominal concentrations of telmisartan and amlodipine stated in Table 1. Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size. (USP 1-Dec-2020)

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 257 nm. For Identification B, use a diode array detector in the range of 200–350 nm.

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

Temperatures

Autosampler: 10°

Column: 30°

Flow rate: 1 mL/min

Injection volume: 20 μL

Run time: NLT 1.5 times the retention time of telmisartan (USP 1-Dec-2020)

System suitability

Sample: Standard solution

[Note—The relative retention times for amlodipine and telmisartan are 0.5 and 1.0, respectively.]

Suitability requirements

Tailing factor: NMT 2.0 for telmisartan; NMT 2.5 for amlodipine

Relative standard deviation: NMT 2.0% for telmisartan and amlodipine

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of telmisartan in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response of telmisartan from the Sample solution

r_S = peak response of telmisartan from the Standard solution

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

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

Calculate the percentage of the labeled amount of amlodipine 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 besylate 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: 90.0%–110.0% each of telmisartan and amlodipine

4 PERFORMANCE TESTS

Change to read:

Dissolution 〈711〉

Test 1

Test for telmisartan

Medium: pH 7.5 phosphate buffer (0.05 M monobasic potassium phosphate and 0.038 M sodium hydroxide in 1 L of water; adjusted with diluted sodium hydroxide solution to a pH of 7.5); 900 mL

Apparatus 2: 75 rpm

Time: 20 min

Buffer, Mobile phase, and Diluent: Prepare as directed in the Assay.

Standard stock solution: 0.9 mg/mL of USP Telmisartan RS in Diluent. [Note—Sonication may be required to aid dissolution.]

Standard solution

For Tablets labeled to contain 80 mg of telmisartan: 0.09 mg/mL of USP Telmisartan RS in Medium from the Standard stock solution

For Tablets labeled to contain 40 mg of telmisartan: 0.045 mg/mL of USP Telmisartan RS in Medium from the Standard stock solution (USP 1-Dec-2020)

Sample solution: Pass a portion of the solution under test through a suitable filter of suitable pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 257 nm

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

Temperatures

Autosampler: 10°

Column: 30°

Flow rate: 1 mL/min

Injection volume: 20 μL

Run time: NLT 1.5 times the retention time of telmisartan (USP 1-Dec-2020)

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

[Note—The relative retention times for amlodipine and telmisartan are 0.5 and 1.0, respectively.] (USP 1-Dec-2020)

Calculate the percentage of the labeled amount of telmisartan dissolved:

Result = (r_U/r_S) × (C_S × D) × V × (1/L) × 100

r_U = peak response of telmisartan from the Sample solution

r_S = peak response of telmisartan from the Standard solution

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

D = dilution factor for the Sample solution, if needed

V = volume of Medium, 900 mL

L = label claim of telmisartan (mg/Tablet)

Test for amlodipine

Medium: 0.01 N hydrochloric acid; 500 mL

Apparatus 2: 75 rpm

Time: 20 min

Mobile phase and Chromatographic system: Proceed as directed in Test 1, Test for telmisartan.

Standard stock solution: 0.7 mg/mL of USP Amlodipine Besylate RS in Medium. [Note—Sonication may be required to aid dissolution.]

Standard solution

For Tablets labeled to contain 10 mg of amlodipine: 0.028 mg/mL of USP Amlodipine Besylate RS in Medium from the Standard stock solution

For Tablets labeled to contain 5 mg of amlodipine: 0.014 mg/mL of USP Amlodipine Besylate RS in Medium from the Standard stock solution (USP 1-Dec-2020)

Sample solution: Pass a portion of the solution under test through a suitable filter of suitable pore size.

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.5

Relative standard deviation: NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of amlodipine dissolved:

Result = (r_U/r_S) × (C_S × D) × V × (1/L) × (M_r1/M_r2) × 100

r_U = peak response of amlodipine from the Sample solution

r = peak response of amlodipine from the Standard solution

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

D = dilution factor for the Sample solution, if needed

V = volume of Medium, 500 mL

L = label claim of amlodipine (mg/Tablet)

M_r1 = molecular weight of amlodipine, 408.88

M_r2 = molecular weight of amlodipine besylate, 567.05

Tolerances: NLT 80% (Q) of the labeled amount each of telmisartan and amlodipine is dissolved.

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

Test for telmisartan

Medium: pH 7.5 phosphate buffer (6.805 g/L of monobasic potassium phosphate and 1.6 g/L of sodium hydroxide in water; adjusted with 5 N sodium hydroxide solution or phosphoric acid to a pH of 7.5); 900 mL

Apparatus 2: 75 rpm

Time: 30 min

Buffer: 1.54 g/L of ammonium acetate in water. Adjust with acetic acid to a pH of 5.0.

Mobile phase: Acetonitrile and Buffer (50:50)

Diluent: 0.01 N hydrochloric acid

Standard stock solution: 0.56 mg/mL of USP Telmisartan RS, prepared as follows. Transfer a quantity of USP Telmisartan RS to a suitable volumetric flask. Add 40% of the total volume of both methanol and Diluent. Sonicate to dissolve. Dilute with Diluent to volume and mix well.

Standard solution

For Tablets labeled to contain 80 mg of telmisartan: 0.09 mg/mL of USP Telmisartan RS in Medium from the Standard stock solution

For Tablets labeled to contain 40 mg of telmisartan: 0.045 mg/mL of USP Telmisartan RS in Medium from the Standard stock solution

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

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 230 nm

Column: 4.6-mm × 15-cm; 5-μm packing L7

Temperatures

Autosampler: 10°

Column: 35°

Flow rate: 1.5 mL/min

Injection volume: 10 μL

Run time: NLT 2 times the retention time of telmisartan

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

[Note—The relative retention times for amlodipine and telmisartan are 0.69 and 1.00, respectively.]

Calculate the percentage of the labeled amount of telmisartan dissolved:

Result = (r_U/r_S) × C_S × V × (1/L) × 100

r_U = peak response of telmisartan from the Sample solution

r_S = peak response of telmisartan from the Standard solution

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

V = volume of Medium, 900 mL

L = label claim of telmisartan (mg/Tablet)

Test for amlodipine

Medium: 0.01 N hydrochloric acid; 500 mL

Apparatus 2: 75 rpm

Time: 30 min

Buffer: 1.54 g/L of ammonium acetate in water. Adjust with acetic acid to a pH of 5.0.

Mobile phase: Acetonitrile and Buffer (40:60)

Standard stock solution: 0.35 mg/mL of USP Amlodipine Besylate RS prepared as follows. Transfer a quantity of USP Amlodipine

Besylate RS to a suitable volumetric flask. Add 5% of the total volume of methanol. Sonicate to dissolve. Dilute with water to volume and mix well.

Standard solution

For Tablets labeled to contain 10 mg of amlodipine: 0.028 mg/mL of USP Amlodipine Besylate RS in Medium from the Standard stock solution

For Tablets labeled to contain 5 mg of amlodipine: 0.014 mg/mL of USP Amlodipine Besylate RS in Medium from the Standard stock solution

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

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 238 nm

Column: 4.6-mm × 15-cm; 5-μm packing L7

Temperatures

Autosampler: 10°

Column: 35°

Flow rate: 1.5 mL/min

Injection volume: 40 μL

Run time: NLT 2.5 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

[Note—The relative retention times for amlodipine and telmisartan are 1.0 and 1.9, respectively.]

Calculate the percentage of the labeled amount of amlodipine dissolved:

Result = (r_U/r_S) × C_S × V × (1/L) × (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)

V = volume of Medium, 500 mL

L = label claim of amlodipine (mg/Tablet)

M_r1 = molecular weight of amlodipine, 408.88

M_r2 = molecular weight of amlodipine besylate, 567.05

Tolerances: NLT 80% (Q) of the labeled amount each of telmisartan and amlodipine is dissolved.

Test 3: If the product complies with this test, the labeling indicates that it meets USP Dissolution Test 3.

Test for telmisartan

Medium: pH 7.5 phosphate buffer (dissolve 6.8 g of monobasic potassium phosphate in 1000 mL of water; adjusted with sodium hydroxide to a pH of 7.5); 900 mL

Apparatus 2: 75 rpm

Time: 30 min

Buffer: Dissolve 2.72 g of monobasic potassium phosphate in 1000 mL of water. Adjust with phosphoric acid to a pH of 2.4.

Mobile phase: Acetonitrile and Buffer (40:60)

Standard stock solution: 0.89 mg/mL of USP Telmisartan RS in methanol. Sonication may be needed to aid dissolution.

Standard solution

For Tablets labeled to contain 80 mg of telmisartan: 0.089 mg/mL of USP Telmisartan RS in Medium from the Standard stock solution

For Tablets labeled to contain 40 mg of telmisartan: 0.045 mg/mL of USP Telmisartan RS in Medium from the Standard stock solution

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

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 237 nm

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

Flow rate: 1 mL/min

Injection volume: 10 μL

Run time: NLT 2 times the retention time of telmisartan

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

[Note—The relative retention times for amlodipine and telmisartan are 0.78 and 1.00, respectively.]

Calculate the percentage of the labeled amount of telmisartan dissolved:

Result = (r_U/r_S) × C_S × V × (1/L) × 100

r_U = peak response of telmisartan from the Sample solution

r_S = peak response of telmisartan from the Standard solution

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

V = volume of Medium, 900 mL

L = label claim of telmisartan (mg/Tablet)

Test for amlodipine

Medium: 0.01 N hydrochloric acid; 500 mL

Apparatus 2: 75 rpm

Time: 15 min

Buffer and Mobile phase: Prepare as directed in Test 3, Test for telmisartan.

Standard stock solution: 0.28 mg/mL of USP Amlodipine Besylate RS prepared as follows. Transfer a quantity of USP Amlodipine

Besylate RS to a suitable volumetric flask. Add about 3% of the total volume of methanol. Sonicate to dissolve. Dilute with Medium to volume and mix well.

Standard solution

For Tablets labeled to contain 10 mg of amlodipine: 0.028 mg/mL of USP Amlodipine Besylate RS in Medium from the Standard stock solution

For Tablets labeled to contain 5 mg of amlodipine: 0.014 mg/mL of USP Amlodipine Besylate RS in Medium from the Standard stock solution

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

Chromatographic system: Proceed as directed in the Test 3, Test for telmisartan except for the Run time.

Run time: NLT 2 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

[Note—The relative retention times for amlodipine and telmisartan are 1.00 and 1.28, respectively.]

Calculate the percentage of the labeled amount of amlodipine dissolved:

Result = (r_U/r_S) × C_S × V × (1/L) × (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)

V = volume of Medium, 500 mL

L = label claim of amlodipine (mg/Tablet)

M_r1 = molecular weight of amlodipine, 408.88

M_r2 = molecular weight of amlodipine besylate, 567.05

Tolerances: NLT 80% (Q) of the labeled amount each of telmisartan and amlodipine is dissolved.

Uniformity of Dosage Units 〈905〉: Meet the requirements

5 IMPURITIES

Change to read:

Organic Impurities

Buffer 1: 0.023 M ammonium acetate in water. Adjust with phosphoric acid to a pH of 5.5.

Solution A: Acetonitrile and Buffer 1 (20:80)

Solution B: Acetonitrile and Buffer 1 (65:35)

Mobile phase: See Table 2.

Table 2

Buffer 2: 0.023 M ammonium acetate in water. Adjust with phosphoric acid to a pH of 2.0.

Diluent: Acetonitrile and Buffer 2 (40:60)

Standard stock solution 1: 0.5 mg/mL of USP Telmisartan RS in Diluent

Standard stock solution 2: 0.17 mg/mL of USP Amlodipine Besylate RS in Diluent

Standard solution: 25 μg/mL of USP Telmisartan RS from Standard stock solution 1 and 4.25 μg/mL of USP Amlodipine Besylate RS from Standard stock solution 2 in Diluent

Sensitivity solution: 0.25 μg/mL of USP Telmisartan RS from Standard stock solution 1 and 0.11 μg/mL of USP Amlodipine Besylate RS from Standard stock solution 2 in Diluent

Sample solution: Nominally 0.25 mg/mL of amlodipine prepared as follows. Transfer a suitable quantity, nominally equivalent to 25 mg of amlodipine from finely powdered Tablets (NLT 10), to a suitable volumetric flask. Add Diluent to 70% of the volume of the flask. Sonicate in cold water for 15 min with intermittent shaking. Dilute with Diluent to volume. Pass a portion of the solution under test through a suitable filter of 0.45-μm pore size.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 257 nm

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

Temperatures

Autosampler: 10°

Column: 30°

Flow rate: 1 mL/min

Injection volume: 20 μL

System suitability

Samples: Standard solution and Sensitivity solution

[Note—The relative retention times for amlodipine and telmisartan are 0.74 and 1.0, respectively.]

Suitability requirements

Tailing factor: NMT 2.5, Standard solution

Relative standard deviation: NMT 5.0%, Standard solution

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

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of amlodipine related compound A (IRA 1-Dec-2020) or amlodipine mannitol adduct in the portion of Tablets taken:

Result = (r_U/r_S) × (C_S/C_U) × (1/F) × (M_r1/M_r2) × 100

r_U = peak response of amlodipine related compound A (IRA 1-Dec-2020) or amlodipine mannitol adduct 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 (μg/mL)

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

F = relative response factor (see Table 3)

M_r1 = molecular weight of amlodipine, 408.88

M_r2 = molecular weight of amlodipine besylate, 567.05

Calculate the percentage of each individual 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 each individual 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 in the Standard solution (μg/mL)

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

M_r1 = molecular weight of amlodipine, 408.88

M_r2 = molecular weight of amlodipine besylate, 567.05

Acceptance criteria: See Table 3. The reporting threshold is 0.1%. (USP 1-Dec-2020)

Table 3

^a Peak due to besylate (benzenesulfonic acid).

^b 3-Ethyl 5-methyl [2-(2-aminoethoxymethyl)-4-(2-chlorophenyl)-6-methyl-3,5-pyridinedicarboxylate] fumarate. (IRA 1-Dec-2020)

^c 1,7′-Dimethyl-2′-propyl-1H,3′H-2,5′-bibenzo[d]imidazole.

^d Process impurities controlled in the drug substance.

^e 4′-[(1,7′-Dimethyl-2′-propyl-1H,1′H-2,5′-bibenzo[d]imidazol-1′-yl)methyl]biphenyl-2-carboxylic acid.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in tight containers. Store at controlled room temperature.

Labeling: When more than one Dissolution test is given, the labeling states the Dissolution test used only if Test 1 is not used.

USP Reference Standards 〈11〉

USP Amlodipine Besylate RS

USP Telmisartan RS