Chlorothiazide 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

Chlorothiazide Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of chlorothiazide (C₇H₆ClN₃O₄S₂).

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 spectrum of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.

3 ASSAY

3.1 PROCEDURE

Solution A: 0.1% formic acid in water Solution B: Methanol

Mobile phase: See Table 1.

Table 1

Diluent: Acetonitrile and Solution A (30:70)

Standard solution: 0.1 mg/mL of USP Chlorothiazide RS in Diluent

Sample stock solution: 0.5 mg/mL of chlorothiazide in Diluent prepared as follows. Transfer a suitable amount of finely powdered Tablets (NLT 20), equivalent to 25 mg of chlorothiazide, to a 50-mL volumetric flask. Add 40 mL of Diluent and sonicate. Dilute with Diluent to volume. Centrifuge and use the supernatant.

Sample solution: Nominally 0.1 mg/mL of chlorothiazide in Diluent from the Sample stock solution

3.1.1 Chromatographic system

(See Chromatography 〈621〉, System Suitability.) Mode: LC

Detector: UV 275 nm. For Identification test B, use a diode array detector in the range of 200–400 nm. Column: 4.6-mm × 15-cm; 5-µm packing L1

Temperatures Autosampler: 5°

Column: 30°

Flow rate: 1 mL/min

Injection volume: 10 µL

3.1.2 System suitability

Sample: Standard solution

Suitability requirements

Tailing factor: NMT 2.0

Relative standard deviation: NMT 1.0%

3.1.3 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of the labeled amount of chlorothiazide (C H ClN O S ) in the portion of Tablets taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of chlorothiazide from the Sample solution

r_s = peak response of chlorothiazide from the Standard solution

C_s = concentration of USP Chlorothiazide RS in the Standard solution (mg/mL)

C_u = nominal concentration of chlorothiazide in the Sample solution (mg/mL)

Acceptance criteria: 90.0%–110.0%

4 PERFORMANCE TESTS

4.1 DISSOLUTION 〈711〉

Medium: 0.05 M pH 8.0 phosphate buffer (see Reagents, Indicators, and Solutions—Buffer Solutions); 900 mL Apparatus 2: 75 rpm

Time: 60 min

Standard solution: Known concentration of USP Chlorothiazide RS in Medium

Sample solution: Filtered portions of the solution under test, suitably diluted with Medium to a concentration that is similar to the Standard solution

Instrumental conditions Mode: UV

Analytical wavelength: 294 nm Analysis

Samples: Standard solution and Sample solution

Tolerances: NLT 75% (Q ) of the labeled amount of chlorothiazide (C₇H₆ClN₃O₄S₂) is dissolved.

4.2 UNIFORMITY OF DOSAGE UNITS 〈905〉

Meet the requirements

5 IMPURITIES

5.1 ORGANIC IMPURITIES

Solution A, Solution B, Mobile phase, Diluent, and Chromatographic system: Proceed as directed in the Assay.

Standard solution: 10 µg/mL of USP Benzothiadiazine Related Compound A RS and 2 µg/mL of USP Chlorothiazide RS in Diluent

Sample solution: Nominally 1 mg/mL of chlorothiazide in Diluent prepared as follows. Transfer a suitable amount of finely powdered Tablets (NLT 20) to an appropriate volumetric flask. Add Diluent to 80% of the final flask volume and sonicate. Dilute with Diluent to volume.

Centrifuge and use the supernatant.

5.1.1 System suitability

Sample: Standard solution

[NOTE—See Table 2 for relative retention times.] Suitability requirements

Resolution: NLT 4.0 between the benzothiadiazine related compound A and chlorothiazide peaks Relative standard deviation: NMT 5.0% for chlorothiazide

5.1.2 Analysis

Samples: Standard solution and Sample solution

Calculate the percentage of each individual unspecified degradation product in the portion of Tablets taken:

Result = (r_u/r_s) × (C_s/C_u) × 100

r_u = peak response of each unspecified degradation product from the Sample solution

r_s = peak response of chlorothiazide from the Standard solution

C_s = concentration of USP Chlorothiazide RS in the Standard solution (µg/mL)

C_u = nominal concentration of chlorothiazide in the Sample solution (µg/mL)

Acceptance criteria: See Table 2. Disregard any peak below 0.05%.

Table 2

^a Not included in the total degradation products.

6 ADDITIONAL REQUIREMENTS

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

USP REFERENCE STANDARDS 〈11〉

USP Benzothiadiazine Related Compound A RS

USP Chlorothiazide RS