Spironolactone and Hydrochlorothiazide Compounded Oral Suspension

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

Spironolactone and Hydrochlorothiazide Compounded Oral Suspension contains NLT 90.0% and NMT 110.0% of the labeled amount of spironolactone (C₂₄H₃₂O₄S) and hydrochlorothiazide (C₇H₈ClN₃O₄S₂).

Prepare an oral suspension containing 5 mg/mL of spironolactone and 5 mg/mL of hydrochlorothiazide as follows (see Pharmaceutical Compounding—Nonsterile Preparations 〈795〉).

^a  Spironolactone and hydrochlorothiazide 25-mg/25-mg tablets, Mylan Pharmaceutical Inc., Morgantown, WV.

^b Paddock Laboratories, Minneapolis, MN.

Calculate the required quantity of each ingredient for the total amount to be prepared. Place the required number of Spironolactone and Hydrochlorothiazide tablets in a suitable mortar, and comminute to a fine powder. Add the Vehicle in small portions, and triturate to make a smooth paste. Add increasing volumes of the Vehicle to make a spironolactoneand hydrochlorothiazide liquid that is pourable. Transfer the contents of the mortar, stepwise and quantitatively, to a calibrated bottle. Add enough of the Vehicle to bring to final volume, and mix well.

2 ASSAY

PROCEDURE

Mobile phase: Methanol and water (70:30). Filter and degas.

Standard solution: 0.1 mg/mL of USP Spironolactone RS and 0.1 mg/mL of USP Hydrochlorothiazide RS in methanol

Sample solution: Shake thoroughly by hand each bottle of Oral Suspension. Prepare 0.1 mg/mL of spironolactone and 0.1 mg/mL of hydrochlorothiazide from Oral Suspension and methanol. Centrifuge.

Chromatographic system

(See Chromatography 〈621〉, System Suitability.)

Mode: LC

Detector: UV 254 nm

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

Flow rate: 1.0 mL/min

Injection volume: 20 µL

System suitability

Sample: Standard solution

[NOTE—The retention times for hydrochlorothiazide and spironolactone are about 3.5 and 7.4 min, respectively.]

Suitability requirements

Relative standard deviation: NMT 2.0% for spironolactone and NMT 2.0% for hydrochlorothiazide for replicate injections Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of spironolactone (C₂₄H₃₂O₄S) in the portion of Oral Suspension taken:

Result = (r_U/r_S) × (C_S/C_U) × 100

r_U = peak response from the Sample solution

r_S = peak response from the Standard solution

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

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

Calculate the percentage of the labeled amount of hydrochlorothiazide (C₇H₈ClN₃O₄S₂) in the portion of Oral Suspension taken by the same formula, changing the terms to refer to hydrochlorothiazide.

Acceptance criteria: 90.0%–110.0%

3 SPECIFIC TESTS

PH 〈791〉: 3.8–4.8

4 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Package in tight, light-resistant containers. Store in a refrigerator or at controlled room temperature.

BEYOND-USE DATE: NMT 60 days after the date on which it was compounded, when stored in a refrigerator or controlled at room temperature

LABELING: Label it to indicate that it is to be well shaken before use, and to state the Beyond-Use Date.

USP REFERENCE STANDARDS 〈11〉

USP Hydrochlorothiazide RS USP Spironolactone RS