Hydrochlorothiazide Capsules
DEFINITION
Hydrochlorothiazide Capsules contain NLT 90.0% and NMT 110.0% of the labeled amount of hydrochlorothiazide (C7H8ClN3O4S2).
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.
ASSAY
• Procedure
Buffer:
13.8 g/L of monobasic sodium phosphate
Mobile phase:
Acetonitrile and Buffer (10:90). Adjust with 10% (v/v) phosphoric acid to a pH of 3.0 ± 0.1. Pass through a filter of 0.45-µm pore size.
System suitability solution:
0.15 mg/mL of each of USP Hydrochlorothiazide RS and USP Chlorothiazide RS in Mobile phase. Sonicate to completely dissolve.
Standard stock solution:
0.50 mg/mL solution prepared as follows: Dissolve a quantity of USP Hydrochlorothiazide RS in acetonitrile (10% of the volume of the flask), and dilute with Mobile phase. Sonicate to completely dissolve.
Standard solution:
50 µg/mL solution in Mobile phase from the Standard stock solution. Sonicate to completely dissolve.
Sample stock solution:
0.25 mg/mL of hydrochlorothiazide solution prepared as follows: Transfer a number of Capsules into a suitable volumetric flask. Add water, 10% of the volume of the flask, and sonicate for 10 min with vigorous shaking. Add Buffer, 20% of the volume of the flask, and again sonicate for 10 min. Add acetonitrile up to 40% of the volume of the flask, and sonicate for 30 min. Dilute with Buffer to volume, and pass through a suitable filter of 0.45-µm pore size.
Sample solution:
50 µg/mL of hydrochlorothiazide in Mobile phase from Sample stock solution
Chromatographic system
Mode:
LC
Detector:
UV 272 nm
Column:
4.6-mm × 25-cm; 5-µm packing L1
Flow rate:
2.0 mL/min
Injection size:
20 µL
System suitability
Samples:
System suitability solution and Standard solution
Suitability requirements
Resolution:
NLT 2.0 between chlorothiazide and hydrochlorothiazide, System suitability solution
Tailing factor:
NMT 2.0, Standard solution
Column efficiency:
NLT 4000 theoretical plates, Standard solution
Relative standard deviation:
NMT 2.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of the labeled amount of hydrochlorothiazide (C7H8ClN3O4S2) in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × 100
Acceptance criteria:
90.0%110.0%
PERFORMANCE TESTS
• Dissolution 711
Medium:
0.1 N hydrochloric acid; 900 mL
Apparatus 1:
100 rpm
Time:
30 min
Standard solution:
6.75-µg/mL solution prepared as follows: Dissolve a quantity of USP Hydrochlorothiazide RS in acetonitrile (10% of the volume of the flask), and dilute with Medium. Sonicate to completely dissolve.
Sample solution:
Pass a portion of the solution under test through a suitable filter of 0.45-µm pore size. Dilute with Medium to a concentration similar to the Standard solution.
Analytical wavelength:
UV 272 nm
Pathlength:
1 cm
Blank:
Medium
Calculate the percentage of the labeled amount of hydrochlorothiazide (C7H8ClN3O4S2) dissolved:
Result = (AU/AS) × (CS/L) × D × V × 100
Tolerances:
NLT 80% (Q) of the labeled amount of hydrochlorothiazide (C7H8ClN3O4S2) is dissolved.
• Uniformity of Dosage Units 905:
Meet the requirements
IMPURITIES
Organic Impurities
• Procedure
Buffer, Mobile phase, System suitability solution, and Chromatographic system:
Proceed as directed in the Assay.
Standard stock solution:
0.25-mg/mL solution prepared as follows: Dissolve a quantity of USP Hydrochlorothiazide RS in acetonitrile (10% of the volume of the flask), and dilute with Mobile phase.
Standard solution:
0.25 µg/mL of USP Hydrochlorothiazide RS in Mobile phase from Standard stock solution
Sample solution:
Use the Sample stock solution as prepared in the Assay.
Suitability requirements
Samples:
System suitability solution and Standard solution
Resolution:
NLT 2.0 between chlorothiazide and hydrochlorothiazide, System suitability solution
Tailing factor:
NMT 2.0, Standard solution
Column efficiency:
NLT 4000 theoretical plates, Standard solution
Relative standard deviation:
NMT 5.0%, Standard solution
Analysis
Samples:
Standard solution and Sample solution
Calculate the percentage of each individual impurity in the portion of Capsules taken:
Result = (rU/rS) × (CS/CU) × (1/F) × 100
Acceptance criteria
Individual impurities:
See Table 1.
Total impurities:
NMT 1.5%.
Table 1
ADDITIONAL REQUIREMENTS
• Packaging and Storage:
Preserve in well-closed containers, and store at controlled room temperature.
Auxiliary Information
Please check for your question in the FAQs before contacting USP.
USP35NF30 Page 3422
Pharmacopeial Forum: Volume No. 36(2) Page 405
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