Drug release 
724
—
Test 1—
If the product complies with this test, the labeling indicates that the product meets USP
Drug Release Test 1.
Medium:
0.1 N hydrochloric acid; 900 mL.
Apparatus 2:
50 rpm.
Times:
1, 4, and 6 hours.
Procedure—
Determine the amount of C
13H
21N
3O·HCl dissolved from UV absorbances at the wavelength of maximum absorbance at about 224 nm, using filtered portions of the solution under test, diluted with
Medium, if necessary, in comparison with a Standard solution having a known concentration of
USP Procainamide Hydrochloride RS in the same
Medium.
Tolerances—
The percentage of the labeled amount of C
13H
21N
3O·HCl dissolved is within the range stated at each of the following times.
| Time (hours) |
 Amount dissolved |
| 1 |
between 30% and 60% |
| 4 |
between 60% and 90% |
| 6 |
not less than 75% |
Test 2—
If the product complies with this test, the labeling indicates that the product meets USP
Drug Release Test 2.
Medium:
Proceed as directed for Method B under Delayed-Release (Enteric-Coated) Articles.
ACID STAGE—
0.1 N hydrochloric acid; 900 mL for 1 hour.
BUFFER STAGE—
0.05 M phosphate buffer, pH 7.5; 900 mL (see Buffer Solutions under Reagents, Indicators, and Solutions) for not less than 8 hours.
Apparatus 2:
50 rpm, with sinkers.
Times:
1, 4, and 8 hours.
Procedure—
Proceed as directed for Procedure in Test 1.
Tolerances—
Proceed as directed for
Interpretation under
Method A, except to employ the criteria in
Acceptance Table 1 instead of
Acceptance Table 3. The percentages of the labeled amount of C
13H
21N
3O·HCl dissolved at the times specified conform to
Acceptance Table 1.
| Time (hours) |
Amount dissolved |
| 1 |
between 30% and 60% |
| 4 |
between 60% and 90% |
| 8 |
not less than 80% |
Test 3—
If the product complies with this test, the labeling indicates that the product meets USP
Drug Release Test 3.
Medium:
Proceed as directed under Test 2.
Apparatus 2:
50 rpm, with sinkers.
Times:
1, 3, 6, and 8 hours.
Procedure—
Proceed as directed for Procedure in Test 1.
Tolerances—
Proceed as directed for
Interpretation under
Method A, except to employ the criteria in
Acceptance Table 1 instead of
Acceptance Table 3. The percentages of the labeled amount of C
13H
21N
3O·HCl dissolved at the times specified conform to
Acceptance Table 1.
| Time (hours) |
Amount dissolved |
| 1 |
between 25% and 50% |
| 3 |
between 40% and 75% |
| 6 |
between 65% and 90% |
| 8 |
not less than 80% |
Test 4—
If the product complies with this test, the labeling indicates that the product meets USP
Drug Release Test 4.
Medium:
0.1 N hydrochloric acid; 900 mL.
Apparatus 1:
50 rpm.
Times:
1, 2, 4, 8, and 14 hours.
Procedure—
Proceed as directed for Procedure in Test 1.
Tolerances—
Proceed as directed for
Interpretation under
Method A, except to employ the criteria in
Acceptance Table 1. The percentages of the labeled amount of C
13H
21N
3O·HCl dissolved at the times specified conform to
Acceptance Table 1.
| Time (hours) |
Amount dissolved |
| 1 |
not more than 30% |
| 2 |
between 25% and 45% |
| 4 |
between 45% and 75% |
| 8 |
between 70% and 90% |
| 14 |
not less than 80% |
Test 5—
If the product complies with this test the labeling indicates that the product meets USP
Drug Release Test 5.
Medium:
Proceed as directed for Method B under Delayed-Release (Enteric-Coated) Articles.
ACID STAGE—
0.1 N hydrochloric acid; 1000 mL for 1 hour.
BUFFER STAGE—
0.05 M phosphate buffer, pH 7.5; 1000 mL (see Buffer Solutions under Reagents, Indicators, and Solutions) for not less than 8 hours.
Apparatus 2:
50 rpm, with sinkers.
Times:
1, 4, 6, and 8 hours.
Procedure—
Proceed as directed for Procedure in Test 1.
Tolerances—
Proceed as directed for Tolerances in Test 2.
FOR 500 MG TABLETS—
| Time (hours) |
Amount dissolved |
| 1 |
between 30% and 45% |
| 4 |
between 55% and 75% |
| 6 |
not less than 65% |
| 8 |
not less than 75% |
FOR 750 AND 1000 MG TABLETS—
| Time (hours) |
Amount dissolved |
| 1 |
between 30% and 50% |
| 4 |
between 60% and 80% |
| 6 |
between 70% and 90% |
| 8 |
not less than 75% |
Test 6:—
If the product complies with this test, the labeling indicates that the product meets USP
Drug Release Test 6.
Medium:
Proceed as directed for Test 2.
Apparatus 2:
50 rpm.
Times:
1, 4, and 8 hours.
Procedure—
Proceed as directed for Procedure in Test 1.
Tolerances—
Proceed as directed for Tolerances in Test 2.
FOR 250 MG TABLETS—
| Time (hours) |
Amount dissolved |
| 1 |
between 30% and 60% |
| 4 |
between 60% and 90% |
| 8 |
not less than 80% |
FOR 500 MG TABLETS—
| Time (hours) |
Amount dissolved |
| 1 |
between 30% and 50% |
| 4 |
between 60% and 80% |
| 8 |
not less than 85% |
FOR 750 MG TABLETS—
| Time (hours) |
Amount dissolved |
| 1 |
between 30% and 50% |
| 4 |
between 60% and 80% |
| 8 |
not less than 80% |
Test 8—
If the product complies with this test, the labeling indicates that the product meets USP
Drug Release Test 8.
Medium:
Proceed as directed for
Method B under
Delayed-Release (
Enteric-Coated)
Articles.
ACID STAGE—
0.1 N hydrochloric acid; 900 mL for 1 hour.
BUFFER STAGE—
0.05 M phosphate buffer, pH 7.5; 900 mL (see Buffer Solutions under Reagents, Indicators, and Solutions) for not less than 8 hours.
Apparatus 2:
50 rpm, with sinkers.
Times:
1, 4, 6, and 8 hours.
Procedure—
Proceed as directed for Procedure in Test 1.
Tolerances—
Proceed as directed for
Tolerances in
Test 2.
| Time (hours) |
Amount dissolved |
| 1 |
between 33% and 50% |
| 4 |
between 70% and 85% |
| 6 |
not less than 80% |
| 8 |
not less than 85% |
Dissolution 711—
Test 1—
If the product complies with this test, the labeling indicates that the product meets USP
Dissolution Test 1.
Medium:
0.1 N hydrochloric acid; 900 mL.
Apparatus 2:
50 rpm.
Times:
1, 4, and 6 hours.
Procedure—
Determine the amount of C
13H
21N
3O·HCl dissolved from UV absorbances at the wavelength of maximum absorbance at about 224 nm, using filtered portions of the solution under test, diluted with
Medium, if necessary, in comparison with a Standard solution having a known concentration of
USP Procainamide Hydrochloride RS in the same
Medium.
Tolerances—
The percentage of the labeled amount of C
13H
21N
3O·HCl dissolved at the times specified conforms to
Acceptance Table 2.
| Time (hours) |
Amount dissolved |
| 1 |
between 30% and 60% |
| 4 |
between 60% and 90% |
| 6 |
not less than 75% |
Test 2—
If the product complies with this test, the labeling indicates that the product meets USP
Dissolution Test 2.
Medium—
Proceed as directed for Method B under Delayed-Release Dosage Forms.
ACID STAGE:
0.1 N hydrochloric acid; 900 mL for 1 hour.
BUFFER STAGE:
0.05 M phosphate buffer, pH 7.5; 900 mL (see Buffer Solutions under Reagents, Indicators, and Solutions) for not less than 8 hours.
Apparatus 2:
50 rpm, with sinkers.
Times:
1, 4, and 8 hours.
Procedure—
Proceed as directed for Procedure in Test 1.
Tolerances—
The percentages of the labeled amount of C
13H
21N
3O·HCl dissolved at the times specified conform to
Acceptance Table 2.
| Time (hours) |
Amount dissolved |
| 1 |
between 30% and 60% |
| 4 |
between 60% and 90% |
| 8 |
not less than 80% |
Test 3—
If the product complies with this test, the labeling indicates that the product meets USP
Dissolution Test 3.
Medium—
Proceed as directed under Test 2.
Apparatus 2:
50 rpm, with sinkers.
Times:
1, 3, 6, and 8 hours.
Procedure—
Proceed as directed for Procedure in Test 1.
Tolerances—
The percentages of the labeled amount of C
13H
21N
3O·HCl dissolved at the times specified conform to
Acceptance Table 2.
| Time (hours) |
Amount dissolved |
| 1 |
between 25% and 50% |
| 3 |
between 40% and 75% |
| 6 |
between 65% and 90% |
| 8 |
not less than 80% |
Test 4—
If the product complies with this test, the labeling indicates that the product meets USP
Dissolution Test 4.
Medium:
0.1 N hydrochloric acid; 900 mL.
Apparatus 1:
50 rpm.
Times:
1, 2, 4, 8, and 14 hours.
Procedure—
Proceed as directed for Procedure in Test 1.
Tolerances—
The percentages of the labeled amount of C
13H
21N
3O·HCl dissolved at the times specified conform to
Acceptance Table 2.
| Time (hours) |
Amount dissolved |
| 1 |
not more than 30% |
| 2 |
between 25% and 45% |
| 4 |
between 45% and 75% |
| 8 |
between 70% and 90% |
| 14 |
not less than 80% |
Test 5—
If the product complies with this test the labeling indicates that the product meets USP
Dissolution Test 5.
Medium—
Proceed as directed for Method B under Delayed-Release Dosage Forms.
ACID STAGE:
0.1 N hydrochloric acid; 1000 mL for 1 hour.
BUFFER STAGE:
0.05 M phosphate buffer, pH 7.5; 1000 mL (see
Buffer Solutions under
Reagents, Indicators, and Solutions) for not less than 8 hours.
Apparatus 2:
50 rpm, with sinkers.
Times:
1, 4, 6, and 8 hours.
Procedure—
Proceed as directed for Procedure in Test 1.
Tolerances—
Proceed as directed for Tolerances in Test 2.
FOR 500 MG TABLETS—
| Time (hours) |
Amount dissolved |
| 1 |
between 30% and 45% |
| 4 |
between 55% and 75% |
| 6 |
not less than 65% |
| 8 |
not less than 75% |
FOR 750 AND 1000 MG TABLETS—
| Time (hours) |
Amount dissolved |
| 1 |
between 30% and 50% |
| 4 |
between 60% and 80% |
| 6 |
between 70% and 90% |
| 8 |
not less than 75% |
Test 6—
If the product complies with this test, the labeling indicates that the product meets USP
Dissolution Test 6.
Medium—
Proceed as directed for Test 2.
Apparatus 2:
50 rpm.
Times:
1, 4, and 8 hours.
Procedure—
Proceed as directed for Procedure in Test 1.
Tolerances—
Proceed as directed for Tolerances in Test 2.
FOR 250 MG TABLETS—
| Time (hours) |
Amount dissolved |
| 1 |
between 30% and 60% |
| 4 |
between 60% and 90% |
| 8 |
not less than 80% |
FOR 500 MG TABLETS—
| Time (hours) |
Amount dissolved |
| 1 |
between 30% and 50% |
| 4 |
between 60% and 80% |
| 8 |
not less than 85% |
FOR 750 MG TABLETS—
| Time (hours) |
Amount dissolved |
| 1 |
between 30% and 50% |
| 4 |
between 60% and 80% |
| 8 |
not less than 80% |
Test 8—
If the product complies with this test, the labeling indicates that the product meets USP
Dissolution Test 8.
Medium—
Proceed as directed for
Method B under
Delayed-Release Dosage Forms.
ACID STAGE:
0.1 N hydrochloric acid; 900 mL for 1 hour.
BUFFER STAGE:
0.05 M phosphate buffer, pH 7.5; 900 mL (see Buffer Solutions under Reagents, Indicators, and Solutions) for not less than 8 hours.
Apparatus 2:
50 rpm, with sinkers.
Times:
1, 4, 6, and 8 hours.
Procedure—
Proceed as directed for Procedure in Test 1.
Tolerances—
Proceed as directed for
Tolerances in
Test 2.
| Time (hours) |
Amount dissolved |
| 1 |
between 33% and 50% |
| 4 |
between 70% and 85% |
| 6 |
not less than 80% |
| 8 |
not less than 85% |
(Official April 1, 2006)
Assay—
Mobile phase—
Prepare a suitable mixture of water, methanol, and triethylamine (140:60:1), adjust with phosphoric acid to a pH of 7.5, filter, and degas. Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Standard preparation—
Dissolve an accurately weighed quantity of
USP Procainamide Hydrochloride RS in
Mobile phase to obtain a solution having a known concentration of about 0.5 mg per mL (
Stock standard solution). Quantitatively dilute an accurately measured volume of this solution with
Mobile phase to obtain a solution having a known concentration of about 0.05 mg per mL (
Standard preparation).
Assay preparation—
Transfer not fewer than 10 Tablets, accurately counted, to a 1000-mL volumetric flask, and add 100 mL of a mixture of methanol and methylene chloride (1:1). Place the flask in a 40
sonicator bath, and sonicate, with occasional shaking, until the Tablets have disintegrated completely. Add about 700 mL of methanol, and sonicate for 10 minutes, with occasional shaking. Allow to cool, dilute with methanol to volume, and mix. Filter a portion of this solution, discarding the first 10 mL of the filtrate. Quantitatively dilute an accurately measured volume of the filtrate with
Mobile phase to obtain a solution having a concentration of about 0.5 mg of procainamide hydrochloride per mL. Use a portion of this stock solution for the
Identification test. Quantitatively dilute another accurately measured volume of the stock solution with
Mobile phase to obtain a solution having a concentration of about 0.05 mg per mL (
Assay preparation).
Resolution solution—
Prepare a solution of p-aminobenzoic acid in Mobile phase containing 0.1 mg per mL. Pipet 10 mL of this solution and 10 mL of the Stock standard into a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 280-nm detector and a 3.9-mm × 30-cm column that contains 10-µm packing L1. The flow rate is about 1 mL per minute. Chromatograph the
Resolution solution: the resolution,
R, is not less than 2.0. Chromatograph replicate injections of the
Standard preparation: the relative standard deviation is not more than 2.0%.
Procedure—
Separately inject equal volumes (about 20 µL) of the
Standard preparation and the
Assay preparation into the chromatograph, record the chromatograms, and measure the responses for the major peaks. The relative retention times are about 0.5 for
p-aminobenzoic acid and 1.0 for procainamide. Calculate the quantity, in mg, of procainamide hydrochloride (C
13H
21N
3O·HCl) per Tablet taken by the formula:
(L / D)(C)(rU / rS),
in which
L is the labeled quantity, in mg, of procainamide hydrochloride in each Tablet;
D is the concentration, in mg per mL, of procainamide hydrochloride in the
Assay preparation, based on the number of Tablets taken, the labeled quantity per Tablet, and the extent of dilution;
C is the concentration, in mg per mL, of
USP Procainamide Hydrochloride RS in the
Standard preparation; and
rU and
rS are the peak responses obtained from the
Assay preparation and the
Standard preparation, respectively.
