Candesartan Cilexetil 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

Candesartan cilexetil Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of candesartan cilexetil (C₃₃H₃₄N₆O₆)

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 absorption spectra of the major peak of the Sample solution exhibit maxima and minima at the same wavelengths as those of the Standard solution, as obtained in the Assay.

3 ASSAY

Change to read:

PROCEDURE

Mobile phase: Acetonitrile and water (55:45). To each liter, add 1.0 mL of trifluoroacetic acid (USP 1-Dec-2022)

Diluent: Acetonitrile and water (70:30)

Standard solution: 0.8 mg/mL of USP Candesartan Cilexetil RS in Diluent. Sonication may be necessary for complete dissolution. (USP 1-Dec-2022)

Sample solution: Nominally 0.8 mg/mL of candesartan cilexetil in Diluent prepared as follows. Transfer a number of Tablets (see Table 1) to a suitable volumetric flask.

Table 1

Add Diluent to about 70% of the total volume and sonicate for about 25 min with intermittent shaking. Allow to cool and dilute with Diluent to volume. Pass through a suitable filter of 0.45-µm pore size.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 282 nm. For Identification B, use a diode array detector in the range of 210-400 nm. (USP 1-Dec-2022)

Column: 4.6-mm x 15-cm; 5-µm packing LZ

Column temperature: 30°

Flow rate: 1.5 mL/min

Injection volume: 10 µL

Run time: NLT 2.7 times the retention time of candesartan cilexetil

System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0% (USP 1-Dec-2022)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of candesartan cilexetil (C₃₃H₃₄N₆O₆) in the portion of Tablets taken:

Result = (r_U/r_S) x (C_S/C_U) ×100

r_U = peak response of candesartan cilexetil (USP 1-Dec-2022) from the Sample solution

r_S = peak response of candesartan cilexetil (USP 1-Dec-2022) from the Standard solution

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

C = nominal concentration of candesartan cilexetil in the Sample solution (mg/mL)

Acceptance criteria: 90.0%-110.0%

4 PERFORMANCE TESTS

Change to read:

DISSOLUTION (711)

Medium

For Tablets labeled to contain 4, 8, or 16 mg: 0.35% polysorbate 20 in 0.05 M phosphate buffer, pH 6.5 (dissolve 6.8 g of potassium phosphate, monobasic in a suitable container containing 500 ml. of water add 3.5 ml. of polysorbate 20 and dilute with water to 1 L adjust with 2 N sodium hydroxide solution to a pH of 6.5) (USP 1-Dec-2022) 900 ml

For Tablets labeled to contain 32 mg: 0.70% polysorbate 20 in 0.05 M phosphate buffer, pH 6.5 (dissolve 6.8 g of potassium phosphate. monobasic in a suitable container containing 500 ml of water, add 7.0 ml. of polysorbate 20 and dilute with water to 1 L; adjust with 2 N sodium hydroxide solution to a pH of 6.5) (USP 1-Dec-2022) 900 ml.

Apparatus 2: 50 rpm

Time: 45 min

Mobile phase: Acetonitrile and water (55:45). To each liter, add 1.0 mL of trifluoroacetic acid (USP 1-Dec-2022)

Standard stock solution: 0.45 mg/ml. of USP Candesartan Cilexetil RS in acetonitrile Sonication may be necessary for complete dissolution.

Standard solution: (L/900) mg/mL of USP Candesartan Cilexetil RS from the Standard stock solution in Medium, where L is the label claim in mg/Tablet (USP 1-Dec-2022) OFFICIA

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

Chromatographic system

(See Chromatography (621). System Suitability)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm x 15-cm; 5-um packing LZ

Column temperature: 30"

Flow rate: 1.5 mL/min

Injection volume: 50 µL

Run time: NLT 1.8 times the retention time of candesartan cilexetil

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 candesartan cilexetil (C₃₃H₃₄N₆O₆) dissolved:

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

r_U = upeak response of candesartan cilexetil (USP 1-Dec-2022) from the Sample solution

r_S = speak response of candesartan cilexetil (USP 1-Dec-2022) from the Standard solution

C_S = concentration of USP Candesartan Cilexetil RS in (USP 1-Dec-2022) the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim (mg/Tablet)

Tolerances: NLT 80% (Q) of the labeled amount of candesartan cilexetil (C₃₃H₃₄N₆O₆) is dissolved.

UNIFORMITY OF DOSAGE UNITS (905): Meet the requirements

5 IMPURITIES

Change to read:

ORGANIC IMPURITIES

Solution A: Acetonitrile and water (10:90). To each liter, add 1.0 mL of trifluoroacetic acid (USP 1-Dec-2022)

Solution B: Acetonitrile and water (90:10). To each liter, add 1.0 ml. of trifluoroacetic acid (USP 1-Dec-2022)

Mobile phase: See Table 2.

Table 2

System suitability stock solution A: 0.05 mg/mL each of USP Candesartan Cilexetil Related Compound A RS, USP Candesartan Cilexetil Related Compound B RS. USP Candesartan Cilexetil Related Compound. D. RS, and USP Candesartan Cilexetil Related Compound F.RS in acetonitrile

System suitability stock solution B: 0.1 mg/mL of USP Candesartan Cilexetil RS in acetonitrile

System suitability stock solution C: 0.5 mg/mL of USP Candesartan Cilexetil Related Compound G. RS in methanol

System suitability solution: 0.0015 mg/mL each of USP. Candesartan Cilexetil Related Compound A RS. USP Candesartan Cilexetil Related Compound B RS, USP Candesartan Cilexetil Related Compound D RS, and USP Candesartan Cilexetil Related Compound FRS: 0.001 mg/mL of USP Candesartan Cilexetil RS; and 0.005 mg/mL of USP Candesartan Cilexetil Related Compound G.RS from System suitability stock solution A, System suitability stock solution B, and System suitability stock solution C in acetonitrile

Standard solution: 0.001 mg/mL of USP Candesartan Cilexetil RS in acetonitrile, from System suitability stock solution B

Sample solution: Nominally 1 mg/mL of candesartan cilexetil in acetonitrile prepared as follows. Transfer a suitable quantity of candesartan cilexetil from NLT 20 powdered Tablets to a suitable volumetric flask. Add acetonitrile to fill 60% of the total volume and sonicate for 15 min with intermittent shaking in cold water. Dilute with acetonitrile to volume and pass through a suitable filter of 0.45-um pore size.

Chromatographic system

(See Chromatography (621), System Suitability)

Mode: LC

Detector: UV 254 nm

Column: 4.6-mm x 10-cm: 3.5-µm packing 11

Autosampler temperature: 10°

Flow rate: 1 ml/min

Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[NOTE-See Table 3 for the relative retention times. (USP 1-Dec-2022)

Suitability requirements

Resolution: NLT 5.0 between candesartan cilexetil and candesartan cilexetil related compound D. (USP 1-Dec-2022) System suitability solution

Tailing factor: NMT 2.0 (USP 1-Dec-2022), Standard solution

Relative standard deviation: NMT 5.0% (USP 1-Dec-2022) Standard solution

Signal-to-noise ratio: NLT 10, Standard solution (USP 1-Dec-2022)

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each specified and unspecified degradation product (USP 1-Dec-2022) In the portion of Tablets taken:

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

r_U = upeak response of each specified or unspecified degradation product (USP 1-Dec-2022) from the Sample solution

r_S = peak response of candesartan cilexetil from the Standard solution

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

C_U = nominal concentration of candesartan cilexetil in the Sample solution (mg/ml)

F = relative response factor of each specified or unspecified degradation product (USP 1-Dec-2022) (see Table 3)

Acceptance criteria: See Table 3. The reporting threshold is 0.1% (USP 1-Dec-2022)

Table 3

Process-related impurity is not included in total degradation products. (USP 1-Dec-2022)

6 ADDITIONAL REQUIREMENTS

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

Change to read:

USP REFERENCE STANDARDS (11)

USP Condesartan Cilexetil RS

USP Candesartan Cilexetil Related Compound A RS

Ethyl 2-ethoxy-1-[2-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl)benzimidazole-7-carboxylate; Also known as (USP 1-Dec-2022) Ethyl 1-([2-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl)-2-ethoxybenzimidazole-7-carboxylate.

C₂₁H₂₄N₆O₃ 468.51

USP. Candesartan Cilentil Related Compound & RS 4.0

1-Cyclohexyloxycarbonyloxyethyl 1-[2-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl)-2-oxo-2,3-dihydrobenzimidazole-7-carboxylate; Also known as (1-([(Cyclohexyloxy) carbonyl]oxy)ethyl 3-((2-(1H-tetrazol-5-yl)-[1,1'-biphenyl-4-yl)methyl)-2-oxo-2,3-dihydro-1H-benzo[d]imidazole-4-carboxylate) (USP 1-Dec-2022)

C₃₁H₃₀N₆O₆ 582.62 (USP 1-Dec-2022)

USP Condesartan Cilexetil Related Compound D.RS

1-[(Cyclohexyloxy)carbonyl)oxy)ethyl 1-([2-(2-ethyl-2H-tetrazol-5-yl)biphenyl-4-yl]methyl)-2-oxo-2,3-dihydrobenzimidazole-7-carboxylate; Also known as 1-{[(Cyclohexyloxy) carbonyl]oxy)ethyl 3-((2-(2-ethyl-2H-tetrazol-5-yl)-[1,1'-biphenyl]-4-yl)methyl)-2-oxo-2,3-dihydro-1H-benzimidazole-4-carboxylate) (USP 1-Dec-2022)

C₃₃H₃₄N₆O₆ 610.67

USP Candesartan Cilexetil Related Compound F RS

1-Cyclohexyloxycarbonyloxyethyl 2-ethoxy-1-{[2’-(2-ethyl-2H-tetrazol-5-yl)biphenyl-4-yl]methyl}benzimidazole-7-carboxylate;

Also known as (1-(Cyclohexyloxycarbonyloxy)ethyl 2-ethoxy-1-{[2'-(2-ethyl-2H-tetrazol-5-yl)biphenyl-4-yl]methyl}-1H-benzimidazole-7-

carboxylate). (USP 1-Dec-2022)

C₃₅H₃₈N₆O₆ 638.73 (USP 1-Dec-2022)

USP Candesartan Cilexetil Related Compound G RS

2-Ethoxy-1-{[2’-(1H-tetrazol-5-yl)biphenyl-4-yl]methyl}benzimidazole-7-carboxylic acid;

Also known as (USP 1-Dec-2022) 1-{[2'-(1H-Tetrazol-5-yl)biphenyl-4-yl]methyl}-2-ethoxybenzimidazole-7-carboxylic acid.

C₂₄H₂₀N₆O₃ 440.46 (USP 1-Dec-2022)