Moexipril Hydrochloride and Hydrochlorothiazide 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

Moexipril Hydrochloride and Hydrochlorothiazide Tablets contain NLT 90.0% and NMT 110.0% each of the labeled amounts of moexipril hydrochloride (C₂₇H₃₄N₂O₇ · HCl) and hydrochlorothiazide (C₇H₈ClN₃O₄S₂).

2 IDENTIFICATION

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

Add the following:

B. The UV spectra of the major peaks of the Diluted sample solution correspond to those of the Diluted standard solution, as obtained in the Assay.

3 ASSAY

Change to read:

3.1 Procedure

Buffer: 0.01 M potassium dihydrogen phosphate

Mobile phase: Acetonitrile and Buffer (35:65)

Diluent: Acetonitrile and water (30:70)

Standard solution: Prepare solutions of USP Moexipril Hydrochloride RS and USP Hydrochlorothiazide RS in Diluent, of concentrations stated in Table 1. Initially add Diluent to 70% of the total volume, sonicate to dissolve, and then dilute with Diluent to volume.

Table 1

Diluted standard solution: Standard solution and Diluent (50:50)

Sample solution: The nominal concentrations of moexipril and hydrochlorothiazide in mg/mL given in Table 1 prepared as follows from powdered Tablets (NLT 20). Initially add Diluent to about 60% of the total volume, sonicate for 45 min with intermittent shaking, and then dilute with Diluent to volume. Pass through a suitable filter of 0.45-µm pore size.

Diluted sample solution: Sample solution and Diluent (50:50)

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 210 nm. For Identification B, use a diode array detector in the range of 200–400 nm.
• Column: 4.6-mm × 25-cm; 5-µm packing L7
• Column temperature: 30°
• Flow rate: 1 mL/min
• Injection volume: 20 µL
• Run time: NLT 2.2 times the retention time of the moexipril peak

System suitability

Sample: Standard solution

[Note-The relative retention times for hydrochlorothiazide and moexipril are 0.43 and 1.00, respectively.]

Suitability requirements 

Tailing factor: NMT 2.0 for both the moexipril and hydrochlorothiazide peaks

Relative standard deviation: NMT 2.0% for both the moexipril and hydrochlorothiazide peaks

Analysis

Samples: Standard solution, Diluted standard solution, Sample solution, and Diluted sample solution

[Note-The Diluted standard solution and Diluted sample solution are used for Identification B.]

Calculate the percentage of the labeled amounts of moexipril hydrochloride (C₂₇H₃₄N₂O₇ · HCl) and hydrochlorothiazide (C₇H₈ClN₃O₄S₂) in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of moexipril or hydrochlorothiazide from the Sample solution

rₛ = peak response of moexipril or hydrochlorothiazide from the Standard solution

Cₛ = concentration of USP Moexipril Hydrochloride RS or USP Hydrochlorothiazide RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of moexipril hydrochloride or hydrochlorothiazide in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0% each of the labeled amounts of moexipril hydrochloride and hydrochlorothiazide

4 PERFORMANCE TESTS

Change to read:

4.1 Dissolution 〈711〉

Medium: 0.1 N hydrochloric acid; 900 mL

Apparatus 2: 50 rpm

Time: 15 min

Buffer, Mobile phase, Chromatographic system, and System suitability: Proceed as directed in the Assay.

Standard solution: Prepare solutions of USP Moexipril Hydrochloride RS and USP Hydrochlorothiazide RS in Medium of concentrations stated in Table 2.

Table 2

Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size, discarding the first 2–3 mL.

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amounts of moexipril hydrochloride (C₂₇H₃₄N₂O₇ · HCl) and hydrochlorothiazide (C₇H₈ClN₃O₄S₂) dissolved:

Result = (rᵤ/rₛ) × Cₛ × V × (1/L) × 100

rᵤ = peak response of moexipril or hydrochlorothiazide from the Sample solution

rₛ = peak response of moexipril or hydrochlorothiazide from the Standard solution

Cₛ = concentration of USP Moexipril Hydrochloride RS or USP Hydrochlorothiazide RS in the Standard solution (mg/mL)

V = volume of Medium, 900 mL

L = label claim for moexipril hydrochloride or hydrochlorothiazide (mg/Tablet)

Tolerances: NLT 70% (Q) of the labeled amounts each of moexipril hydrochloride (C₂₇H₃₄N₂O₇ · HCl) and hydrochlorothiazide (C₇H₈ClN₃O₄S₂) are dissolved.

4.2 Uniformity of Dosage Units 〈905〉

Meet the requirements

5 IMPURITIES

Change to read:

5.1 Organic Impurities

Solution A: Add 1 mL of trifiuoroacetic acid to 4 L of water.

Solution B: Acetonitrile and tetrahydrofuran (90:10)

Mobile phase: See Table 3.

Table 3

Diluent: Prepare as directed in the Assay.

System suitability solution: 1.2 mg/mL of USP Moexipril Hydrochloride RS, 2 mg/mL of USP Hydrochlorothiazide RS, and 2.4 µg/mL of USP Moexipril Related Compound G RS in Diluent. Initially add Diluent to 70% of the total volume, sonicate to dissolve, and then dilute with Diluent to volume.

Standard solution: 1.2 µg/mL of USP Moexipril Hydrochloride RS, 12 µg/mL each of USP Moexipril Related Compound A RS and USP Moexipril Related Compound B RS, 2 µg/mL of USP Hydrochlorothiazide RS, and 40 µg/mL each of USP Benzothiadiazine Related Compound A RS and USP Chlorothiazide RS in Diluent. Initially add Diluent to 70% of the total volume, sonicate to dissolve, and then dilute with Diluent to volume.

Sample solution: The nominal concentrations of moexipril and hydrochlorothiazide in mg/mL given in Table 4 prepared as follows. Initially add Diluent to 70% of the total volume, and sonicate for 15 min with intermittent shaking in ice cold water. Dilute with Diluent to volume, and pass through a suitable filter of 0.45-µm pore size.

Table 4

Chromatographic system

• (See Chromatography 〈621〉, System Suitability.)
• Mode: LC
• Detector: UV 210 nm
• Column: 4.6-mm × 25-cm; 5-µm packing L1
• Column temperature: 30°
• Flow rate: 1 mL/min
• Injection volume: 10 µL

System suitability

Samples: System suitability solution and Standard solution

[Note-See Table 5 for the relative retention times.]

Suitability requirements:

Resolution: NLT 2.5 between the moexipril and moexipril related compound G peaks, System suitability solution

Tailing factor: NMT 2.0 for both the moexipril and hydrochlorothiazide peaks, Standard solution

Relative standard deviation: NMT 5.0% for both the moexipril and hydrochlorothiazide peaks, Standard solution

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of moexipril related compound A or moexipril related compound B in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of moexipril related compound A or moexipril related compound B from the Sample solution

rₛ = peak response of moexipril related compound A or moexipril related compound B from the Standard solution

Cₛ = concentration of USP Moexipril Related Compound A RS or USP Moexipril Related Compound B RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of moexipril hydrochloride in the Sample solution (mg/mL)

Calculate the percentage of benzothiadiazine related compound A or chlorothiazide in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of benzothiadiazine related compound A or chlorothiazide from the Sample solution

rₛ = peak response of benzothiadiazine related compound A or chlorothiazide from the Standard solution

Cₛ = concentration of USP Benzothiadiazine Related Compound A RS or USP Chlorothiazide RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of hydrochlorothiazide in the Sample solution (mg/mL)

Calculate the percentage of any other individual impurity in the portion of Tablets taken:

Result = (rᵤ/rₛ) × (Cₛ/Cᵤ) × 100

rᵤ = peak response of any other individual impurity from the Sample solution

rₛ = peak response of moexipril from the Standard solution

Cₛ = concentration of USP Moexipril Hydrochloride RS in the Standard solution (mg/mL)

Cᵤ = nominal concentration of moexipril hydrochloride in the Sample solution (mg/mL)

Acceptance criteria: See Table 5.

Table 5 

ᵃ (S)-6,7-Dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid.

ᵇ Process-related impurity controlled in the drug substance.

ᶜ (S)-2-[(S)-1-Ethoxy-1-oxo-4-phenylbutan-2-ylamino]propanoic acid.

ᵈ 5,6-Dichloro-3,4-dihydro-2H-benzothiadiazine-7-sulfonamide 1,1-dioxide.

ᵉ (S)-2-{(S)-2-[(S)-4-Cyclohexyl-1-ethoxy-1-oxobutan-2-ylamino]propanoyl}-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid.

ᶠ (S)-tert-Butyl 2-{(S)-2-[(S)-1-ethoxy-1-oxo-4-phenylbutan-2-ylamino]propanoyl}-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylate.

ᵍ Total impurities is a sum total of all specified and unspecified impurities.

6 ADDITIONAL REQUIREMENTS

Packaging and Storage: Preserve in well-closed containers, and protect from light. Store at controlled room temperature.

Change to read:

USP Reference Standards 〈11〉

USP Benzothiadiazine Related Compound A RS

4-Amino-6-chloro-1,3-benzenedisulfonamide.

C₆H₈ClN₃O₄S₂ 285.73

USP Chlorothiazide RS

6-Chloro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide.

C₇H₆ClN₃O₄S₂ 295.73

USP Hydrochlorothiazide RS

USP Moexipril Hydrochloride RS

USP Moexipril Related Compound A RS

(3S)-2-{(2S)-N-[(1S)-1-Carboxy-3-phenylpropyl]alanyl}-1,2,3,4-tetrahydro-6,7-dimethoxy-3-isoquinolinecarboxylic acid.

C₂₅H₃₀N₂O₇ 470.51

USP Moexipril Related Compound B RS

(S)-Ethyl 2-{(3S,11aS)-8,9-dimethoxy-3-methyl-1,4-dioxo-3,4-dihydro-1H-pyrazino[1,2-b]isoquinolin-2(6H,11H,11aH)-yl}-4-phenylbutanoate.

C₂₇H₃₂N₂O₆ 480.55

USP Moexipril Related Compound G RS

(S)-6,7-Dimethoxy-2-{(S)-2-[(S)-1-methoxy-1-oxo-4-phenylbutan-2-ylamino]propanoyl}-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid.

C₂₆H₃₂N₂O₇ 484.54