Triamterene and Hydrochlorothiazide Tablets
» Triamterene and Hydrochlorothiazide Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amounts of triamterene (C12H11N7) and hydrochlorothiazide (C7H8ClN3O4S2).
[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. ]
Packaging and storage—
Preserve in tight, light-resistant containers.
USP Reference standards 
11
—
11—
USP Benzothiadiazine Related Compound A RS 
4-Amino-6-chloro-1,3-benzenedisulfonamide.
C6H8ClN3O4S2 285.73
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4-Amino-6-chloro-1,3-benzenedisulfonamide.
C6H8ClN3O4S2 285.73
USP Hydrochlorothiazide RS
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USP Triamterene RS
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Identification—
A:
The retention times of the major peaks in the chromatogram of the Assay preparation correspond to those in the chromatogram of the Standard preparation, as obtained in the Assay.
B:
Dissolve a portion of finely ground Tablets, equivalent to about 50 mg of triamterene, in 25 mL of methoxyethanol, mix, and filter. Use the filtrate as the Test solution. Prepare Standard solutions containing 1.5 mg of USP Triamterene RS per mL of methoxyethanol (Standard solution 1) and containing 1 mg of USP Hydrochlorothiazide RS per mL of methoxyethanol (Standard solution 2). Separately apply 2 µL of the Test solution and 2 µL each of Standard solution 1 and Standard solution 2 to a suitable thin-layer chromatographic plate (see Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Dry the spots with a current of air. Develop the plate in a solvent system consisting of a mixture of ethyl acetate, glacial acetic acid, and water (8:1:1) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, and allow to dry. Locate the spots under short-wavelength and long-wavelength UV light: the intensity and the RF value of the principal spots obtained from the Test solution correspond to those from Standard solution 1 and Standard solution 2.
621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Dry the spots with a current of air. Develop the plate in a solvent system consisting of a mixture of ethyl acetate, glacial acetic acid, and water (8:1:1) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, and allow to dry. Locate the spots under short-wavelength and long-wavelength UV light: the intensity and the RF value of the principal spots obtained from the Test solution correspond to those from Standard solution 1 and Standard solution 2.
Dissolution 711—
711—
Medium:
0.1 N hydrochloric acid; 900 mL.
Apparatus 2:
75 rpm.
Time:
30 minutes.
Determine the amount of triamterene and hydrochlorothiazide dissolved using the following method.
Buffer solution, Mobile phase, and Chromatographic system—
Proceed as directed in the Assay.
Procedure—
Inject a volume (about 10 µL) of a filtered portion of the solution under test into the chromatograph, record the chromatogram, and measure the responses for the major peaks. Calculate the amounts of triamterene (C12H11N7) and hydrochlorothiazide (C7H8ClN3O4S2) dissolved by comparison with a Standard solution having known concentrations of USP Triamterene RS and USP Hydrochlorothiazide RS in the same Medium and similarly chromatographed.
Tolerances—
Not less than 80% (Q) each of the labeled amounts of C12H11N7 and C7H8ClN3O4S2 is dissolved in 30 minutes.
Uniformity of dosage units 905:
meet the requirements for Content Uniformity with respect to triamterene and to hydrochlorothiazide.
905:
meet the requirements for Content Uniformity with respect to triamterene and to hydrochlorothiazide.
Related compounds—
Solution A—
Dissolve 0.68 g of sodium acetate trihydrate in 100.0 mL of water, adjust with glacial acetic acid to a pH of 5.0, and mix.
Solution B—
Prepare a mixture of acetonitrile and methanol (75:25).
Mobile phase—
Prepare a suitable filtered and degassed mixture of Solution A and Solution B (90:10). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Standard solution—
Prepare a solution of USP Benzothiadiazine Related Compound A RS in acetonitrile having a known concentration of 0.15 mg per mL. Transfer 10.0 mL of this solution to a 100-mL volumetric flask, add 50 mL of acetonitrile and 6 mL of glacial acetic acid, dilute with water to volume, and mix.
Test solution—
Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 150 mg of hydrochlorothiazide, to a 100-mL volumetric flask. Add 60 mL of acetonitrile and 6 mL of glacial acetic acid, and sonicate for 10 minutes. Cool, dilute with water to volume, mix, and filter.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 273-nm detector and a 3.9-mm × 30-cm column that contains 10-µm packing L1. The flow rate is about 2 mL per minute. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0%.
621)—
The liquid chromatograph is equipped with a 273-nm detector and a 3.9-mm × 30-cm column that contains 10-µm packing L1. The flow rate is about 2 mL per minute. Chromatograph the Standard solution, and record the peak responses as directed for Procedure: the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 10 µL) of the Standard solution and the Test solution into the chromatograph, record the chromatograms, and measure the peak areas due to benzothiadiazine related compound A in the Standard solution and the Test solution. The retention times, relative to benzothiadiazine related compound A, are about 1.5 for hydrochlorothiazide and about 10 for triamterene. Calculate the quantity, in mg, of benzothiadiazine related compound A in the hydrochlorothiazide contained in the portion of Tablets taken by the formula:
100C(rU / rS)
in which C is the concentration, in mg per mL, of USP Benzothiadiazine Related Compound A RS in the Standard solution; and rU and rS are the peak areas of benzothiadiazine related compound A obtained from the Test solution and the Standard solution, respectively: not more than 1.0% is present.
Assay—
Buffer solution—
Transfer 6.9 g of monobasic sodium phosphate and 1.43 g of propylamine hydrochloride to a 1000-mL volumetric flask, dissolve in about 900 mL of water, adjust with 1 N sodium hydroxide to a pH of 5.5, dilute with water to volume, and mix.
Mobile phase—
Prepare a filtered and degassed mixture of Buffer solution and acetonitrile (80:20). Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Solvent mixture—
Prepare a mixture of water, acetonitrile, and glacial acetic acid (85:10:5).
Standard preparation—
Transfer about 25 mg of USP Hydrochlorothiazide RS, accurately weighed, to a 100-mL volumetric flask. Add 25J mg of USP Triamterene RS, accurately weighed, J being the ratio of the labeled amount, in mg, of triamterene to the labeled amount, in mg, of hydrochlorothiazide per Tablet. Add 10 mL of acetonitrile, 10 mL of water, and 5 mL of glacial acetic acid, sonicating for 2 to 3 minutes after each addition. Cool to room temperature, dilute with water to volume, and mix.
Assay preparation—
Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 50 mg of hydrochlorothiazide, to a 200-mL volumetric flask. Add about 100 mL of Solvent mixture, place the volumetric flask in a sonic bath heated to between 45
and 50, and sonicate for about 30 minutes. Remove the flask from the bath, and carefully add 70 mL of Solvent mixture. Allow to cool to room temperature, and dilute with Solvent mixture to volume. Filter the solution, discarding the first few mL of the filtrate.
and 50, and sonicate for about 30 minutes. Remove the flask from the bath, and carefully add 70 mL of Solvent mixture. Allow to cool to room temperature, and dilute with Solvent mixture to volume. Filter the solution, discarding the first few mL of the filtrate.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 280-nm detector and a 4.0-mm × 25-cm column that contains packing L1. The flow rate is about 1.2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.65 for hydrochlorothiazide and 1.0 for triamterene; the resolution, R, between hydrochlorothiazide and triamterene is not less than 3.0; and the relative standard deviation for replicate injections is not more than 2.0%.
621)—
The liquid chromatograph is equipped with a 280-nm detector and a 4.0-mm × 25-cm column that contains packing L1. The flow rate is about 1.2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the relative retention times are about 0.65 for hydrochlorothiazide and 1.0 for triamterene; the resolution, R, between hydrochlorothiazide and triamterene is not less than 3.0; and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 10 µL) of the Standard preparation and the Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. Separately calculate the quantities, in mg, of triamterene (C12H11N7) and hydrochlorothiazide (C7H8ClN3O4S2) in the portion of Tablets taken by the formula:
200C(rU / rS)
in which C is the concentration, in mg per mL, of the relevant USP Reference Standard in the Standard preparation; and rU and rS are the peak responses of the relevant analyte obtained from the Assay preparation and the Standard preparation, respectively.
Auxiliary Information—
Please check for your question in the FAQs before contacting USP.
| Topic/Question | Contact | Expert Committee |
|---|---|---|
| Monograph | Sujatha Ramakrishna, Ph.D.
Senior Scientific Liaison 1-301-816-8349 |
(SM22010) Monographs - Small Molecules 2 |
| Reference Standards | RS Technical Services 1-301-816-8129 rstech@usp.org |
|
| 711 |
Margareth R.C. Marques, Ph.D.
Senior Scientific Liaison 1-301-816-8106 |
(GCDF2010) General Chapters - Dosage Forms |
USP35–NF30 Page 4934
Pharmacopeial Forum: Volume No. 29(3) Page 672