Chlorothiazide 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

Chlorothiazide Oral Suspension contains 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 Oral Suspension, equivalent to 25 mg of chlorothiazide, to a 50-mL volumetric flask. Add 40 mL of Diluent and sonicate to dissolve. Dilute with Diluent to volume. Centrifuge and use the supernatant.

Sample solution: Nominally 0.1 mg/mL of chlorothiazide in Diluent, from 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 (C₇H₆ClN₃O₄S₂) in the portion of Oral Suspension 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 UNIFORMITY OF DOSAGE UNITS 〈905〉

For single-unit containers

Acceptance criteria: Meets the requirements

4.2 DELIVERABLE VOLUME 〈698〉

For multiple-unit containers

Acceptance criteria: Meets 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 Oral Suspension, equivalent to 25 mg of chlorothiazide, to a 25-mL volumetric flask. Add 20 mL of Diluent and sonicate to dissolve. 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 Oral Suspension 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 SPECIFIC TESTS

PH 〈791〉: 3.2–4.0

7 ADDITIONAL REQUIREMENTS

PACKAGING AND STORAGE: Preserve in tight containers. Protect from freezing and store at controlled room temperature.

USP REFERENCE STANDARDS 〈11〉

USP Benzothiadiazine Related Compound A RS

USP Chlorothiazide RS