TEST 1:
If the product complies with this test, the labeling indicates that it meets USP
Dissolution Test 1.
Medium:
0.1 M acetic acid containing 1% polysorbate 20; 900 mL.
Apparatus 2:
100 rpm.
Time:
120 minutes.
Procedure—
Determine the amounts of triamterene (C
12H
11N
7) and hydrochlorothiazide (C
7H
8ClN
3O
4S
2) dissolved from UV absorption at the wavelength of maximum absorbance at about 357 nm for triamterene and 271 nm for hydrochlorothiazide (corrected for interference from triamterene on the basis of the absorbances of triamterene at 271 nm and 357 nm) on a filtered portion of the solution under test, suitably diluted with water, in comparison with a Standard solution having known concentrations of
USP Triamterene RS and
USP Hydrochlorothiazide RS in the same
Medium.
Tolerances—
Not less than 80% (Q) of the labeled amounts of C12H11N7 and C7H8ClN3O4S2 is dissolved in 120 minutes.
TEST 2:
If the product complies with this test, the labeling indicates that it meets USP
Dissolution Test 2.
Medium:
4.0% tetrasodium ethylenediaminetetraacetate, 2.0% polysorbate 40, 0.05% pancreatin; 900 mL. Prepare a solution using the following procedure. Add the polysorbate 40 and the tetrasodium ethylenediaminetetraacetate to water, and mix thoroughly. Adjust with phosphoric acid to a pH of 8.0 ± 0.05. Heat to 37
, and add the pancreatin powder. Mix thoroughly, and transfer immediately to the dissolution vessel.
Apparatus 1
(use 10-mesh baskets): 100 rpm.
Time:
8 hours.
Mobile phase—
Prepare a filtered and degassed solution of 0.08 M monobasic sodium phosphate buffer and methanol (3:1). Make adjustments if necessary (see
System Suitability under
Chromatography 
621
).
Standard preparation—
Transfer about 110 mg of
USP Triamterene RS and about 55 mg of
USP Hydrochlorothiazide RS, each accurately weighed, to a 500-mL volumetric flask. Add 100 mL of methanol, sonicate for 10 minutes, and heat in a steam bath until completely dissolved. Dilute with
Medium to volume, and mix. Transfer 25 mL of this solution into a 100-mL volumetric flask, dilute with
Medium to volume, and mix gently to minimize foaming.
Test preparation—
Filter a portion of the solution under test. [NOTE—Do not use nylon filters.]
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 254-nm detector, a guard column that contains packing L7, and an analytical 3.9-mm × 30-cm column that contains packing L11. The flow rate is about 2 mL per minute. Chromatograph the
Standard preparation, and record the responses as directed for
Procedure: the resolution,
R, between the triamterene and hydrochlorothiazide peaks is not less than 2.0; and the relative standard deviation for replicate injections of each analyte is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 50 µL) of the
Standard preparation and the
Test preparation in the chromatograph, record the chromatograms, and measure the responses for the major peaks. Calculate the quantities, in mg, of triamterene (C
12H
11N
7) and hydrochlorothiazide (C
7H
8ClN
3O
4S
2) dissolved by the formula:
900C(rU / rS),
in which
C is the concentration, in mg per mL, of the appropriate USP Reference Standard in the
Standard preparation; and
rU and
rS are the peak responses of the relevant analyte obtained from the
Test preparation and the
Standard preparation, respectively.
Tolerances—
Not less than 70% (Q) of the labeled amount of C12H11N7 and not less than 80% (Q) of the labeled amount of C7H8ClN3O4S2 are dissolved in 8 hours.
TEST 3:
If the product complies with this test, the labeling indicates that it meets USP
Dissolution Test 3.
Medium:
0.1 N hydrochloric acid; 900 mL.
Apparatus 1:
100 rpm.
Time:
45 minutes.
Procedure—
Proceed as directed for Test 1.
Tolerances—
Not less than 75% (Q) of the labeled amounts of C12H11N7 and C7H8ClN3O4S2 is dissolved in 45 minutes.
