Triamterene 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

Triamterene and Hydrochlorothiazide Tablets contain NLT 90.0% and NMT 110.0% of the labeled amounts of triamterene (C₁₂H₁₁N₇) and hydrochlorothiazide (C₇H₈CIN₃O₄S₂).

[NOTE-The Capsules and Tablets dosage forms should not be considered bioequivalent. If patients are to be transferred from one dosage form to the other, retitration and appropriate changes in dosage may be necessary.]

2 IDENTIFICATION

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A. The retention times of the major peaks (USP 1-Dec-2019) of the Sample solution correspond to those of _{(USP 1-Dec-2019)} the Standard solution, as obtained in the Assay.

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B. The UV spectra of the major peaks of the Sample solution correspond to those of the Standard solution, as obtained in the Assay _{(USP 1-Dec-2019)}

3 ASSAY

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PROCEDURE

Buffer: Dissolve 0.82 g of sodium acetate anhydrous in 1000 mL of water, and adjust with glacial acetic acid to a pH of 4.5. _{(USP 1-Dec-2019)}

Mobile phase: Acetonitrile and Buffer (35:65) _{(USP 1-Dec-2019)}

Diluent: Acetonitrile, glacial acetic acid, and water (350:35:650)

System suitability stock solution: 1.5 µg/mL of USP Benzothiadiazine Related Compound A RS in Diluent. Sonicate the solution to aid the dissolution.

Standard stock solution: 0.75 mg/mL of USP Triamterene RS and 0.50 mg/mL of USP Hydrochlorothiazide RS in Diluent. Sonicate the solution to aid the dissolution.

System suitability solution: 22.5 µg/mL of USP Triamterene RS, 15 µg/mL of USP Hydrochlorothiazide RS, and 0.075 µg/mL of USP Benzothiadiazine Related Compound A RS from the Standard stock solution and System suitability stock solution, diluted with Mobile phase

Standard solution: 0.023 mg/mL of USP Triamterene RS and 0.015 mg/mL of USP Hydrochlorothiazide RS in Mobile phase from Standard stock solution

Sample stock solution: Nominally 0.5 mg/mL of hydrochlorothiazide in Diluent prepared as follows. Transfer a suitable number of Tablets (NLT 10) to a suitable volumetric flask. Add Diluent to 80% of the flask volume and sonicate for 30 min. Dilute with Diluent to volume. Centrifuge and use the supernatant. _{(USP 1-Dec-2019)}

Sample solution: Nominally 0.015 mg/mL of hydrochlorothiazide from the Sample stock solution, diluted with Mobile phase _{(USP 1-Dec-2019)}

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 272 nm. For Identification B, use a diode array detector in the range of 190-400 nm. _{(USP 1-Dec-2019)}

Column: 4.6-mm x 25-cm; 5-um packing L1 _{(USP 1-Dec-2019)}

Flow rate: 1 mL/min _{(USP 1-Dec-2019)}

Injection volume: 420 µL

Run time: NLT 2 times the retention time of hydrochlorothiazide _{(USP 1-Dec-2019)}

System suitability

Samples: System suitability solution and Standard solution

[Note—The relative retention times for benzothiadiazine related compound A and hydrochlorothiazide are 0.93 and 1.0, respectively.] _{(USP 1-Dec-2019)}

Suitability requirements

Resolution: NLT 1.5 between hydrochlorothiazide and benzothiadiazine related compound A, System suitability solution (USP 1-Dec-2019)

Relative standard deviation: NMT 2.0%, Standard solution _{(USP 1-Dec-2019)}

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amounts of triamterene (C₁₂H₁₁N₇) and hydrochlorothiazide (C₇H₈CIN₃O₄S₂) in the portion of Tablets taken:

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

r_u = peak response of triamterene or hydrochlorothiazide from the Sample solution

r_s = peak response of triamterene or hydrochlorothiazide from the Standard solution

C_s = concentration of USP Triamterene RS or USP Hydrochlorothiazide RS _{(USP 1-Dec-2019)} in the Standard solution (mg/mL)

C_u = nominal concentration of triamterene or hydrochlorothiazide in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

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DISSOLUTION (711)

Medium: 0.1 N hydrochloric acid: 900 mL

Apparatus 2: 75 rpm

Time: 30 min

Buffer: Transfer 6.9 g of monobasic sodium phosphate and 1.43 g of propylamine hydrochloride to a 1-L volumetric flask. Dissolve in 900mL of water, adjust with 1 N sodium hydroxide to a pH of 5.5, and dilute with water to volume.

Mobile phase: Acetonitrile and Buffer (20:80) _{(USP 1-Dec-2019)}

Standard solution: USP Triamterene RS and USP Hydrochlorothiazide RS in Medium

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

Chromatographic system

(See Chromatography (621) System Suitability.)

Mode: LC

Detector: UV 280 nm

Column: 4.0-mm x 25-cm; packing L1

Flow rate: 1.2 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

[NOTE-The relative retention times for hydrochlorothiazide and triamterene are 0.65 and 1.0, respectively.]

Suitability requirements

Resolution: NLT 3.0 between hydrochlorothiazide and triamterene

Relative standard deviation: NMT 2.0% _{(USP 1-Dec-2019)}

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amounts of triamterene (C₁₂H₁₁N₇) and hydrochlorothiazide (C₇H₈CIN₃O₄S₂) dissolved:

Result = (r_u /r_s ) × (C_s /L) × V × 100

r_u = peak response of triamterene or hydrochlorothiazide from the Sample solution

r_s = peak response of triamterene or hydrochlorothiazide from the Standard solution

C_s = concentration of USP Triamterene RS or USP Hydrochlorothiazide RS in the Standard solution (mg/mL)

L = label claim (mg/Tablet)

V = volume of Medium, 900 mL (USP 1-Dec-2019)

Tolerances: NLT 80% (Q) of the labeled amounts of triamterene (C₁₂H₁₁N₇) and hydrochlorothiazide (C₇H₈CIN₃O₄S₂) is dissolved.

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Uniformity of Dosage Units 〈905〉, Content Uniformity: Meet the requirements _{(USP 1-Dec-2019)}

5 IMPURITIES

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ORGANIC IMPURITIES

Solution A: 6.8 mg/mL of sodium acetate trihydrate in water. Adjust with glacial acetic acid to a pH of 5.0.

Solution B: Acetonitrile and methanol (75:25)

Mobile phase: Solution B and Solution A (10:90)

Standard stock solution: (USP 1-Dec-2019) 0.15 mg/mL of USP Benzothiadiazine Related Compound A RS in acetonitrile

Standard solution: 0.015 mg/mL of USP Benzothiadiazine Related Compound A RS prepared as follows. _{(USP 1-Dec-2019)} Transfer 10.0 mL of the Standard stock solution to a 100-ml volumetric flask, add 50 mL of acetonitrile and 6 mL of glacial acetic acid, and dilute with water to volume.

Sample solution: Nominally 1.5 mg/mL of hydrochlorothiazide prepared as follows. _{(USP 1-Dec-2019)} Transfer an equivalent to 150 mg of hydrochlorothiazide from powdered Tablets (NLT 20) to a 100-mL volumetric flask. Add 60 mL of acetonitrile and 6 mL of glacial acetic acid, and sonicate for 10 min, Cool, and dilute with water to volume.

Chromatographic system

(See Chromatography (621), System Suitability.)

Mode: LC

Detector: UV 273 nm

Column: 3.9-mm x 30-cm; 10-µm packing L1

Flow rate: 2 mL/min

Injection volume: 10 µL

System suitability

Sample: Standard solution

[ NOTE-The relative retention times for benzothiadiazine related compound A, hydrochlorothiazide, and triamterene are about 1.0, 1.5, and 10, respectively. _{(USP 1-Dec-2019)}]

Suitability requirements

Relative standard deviation:

NMT 2.0%

Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of benzothiadiazine related compound A in the hydrochlorothiazide contained in the portion of Tablets taken:

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

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

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

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

C_u = nominal concentration of hydrochlorothiazide in the Sample solution _{(USP 1-Dec-2019)} (mg/mL)

Acceptance criteria: NMT 1.0% of benzothiadiazine related compound A

6 ADDITIONAL REQUIREMENTS

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Packaging and Storage: Preserve in tight, light-resistant containers. Store at controlled room temperature. _{(USP 1-Dec-2019)}

USP Reference Standards 〈11〉

USP Benzothiadiazine Related Compound A RS

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

C₆H₈ClN₃O₄S₂           285.73

USP Hydrochlorothiazide RS

USP Triamterene RS