Dissolution 
711
—
Medium:
0.1 N hydrochloric acid; 900 mL, deaerated.
Apparatus 2:
50 rpm.
Time:
30 minutes.
Standard stock solution—
Transfer about 70 mg of
USP Nefazodone Hydrochloride RS, accurately weighed, to a 50-mL volumetric flask. Add 2.5 mL of methanol, dilute with
Medium to volume, and mix.
Standard solution—
Dilute the Standard stock solution with Medium in such a way that the final concentration is similar to the one expected in the Test solution.
Test solution—
Use portions of the solution under test passed through a 0.45-µm PVDF filter, discarding the first 5 mL.
Procedure—
Determine the percentage of the labeled amount of nefazodone hydrochloride dissolved by employing UV absorption, using a suitable spectrophotometer, at the wavelength of maximum absorbance at about 246 nm, on the
Test solution in comparison with the
Standard solution, using
Medium as the blank. Calculate the percentage of nefazodone hydrochloride (C
25H
32ClN
5O
2·HCl) dissolved by the formula:
in which
AU and
AS are the absorbances obtained from the
Test solution and the
Standard solution, respectively;
CS is the concentration, in mg per mL, of
USP Nefazodone Hydrochloride RS in the
Standard solution; 900 is the volume, in mL, of
Medium; 100 is the conversion factor to percentage; and
LC is the tablet label claim, in mg.
Tolerances—
Not less than 75% (Q) of the labeled amount of C25H32ClN5O2·HCl is dissolved in 30 minutes.
Related compounds—
Dilute acetic acid, Buffer solution, and Mobile phase—
Proceed as directed in the Assay.
System suitability solution—
Transfer about 10 mg of
USP Nefazodone Hydrochloride RS into a 10-mL volumetric flask. Add 2.0 mL of
Nefazodone related compound A stock solution and 2.0 mL of
Nefazodone related compound B stock solution, and mix to dissolve the nefazodone hydrochloride. Dilute with
Mobile phase to volume, and mix.
Standard solution—
Use the Standard preparation, prepared as directed in the Assay.
Test solution—
Use the Assay stock preparation, prepared as directed in the Assay.
Chromatographic system—
Prepare as directed in the
Assay. Chromatograph the
System suitability solution, and record the peak responses as directed for
Procedure. Identify the peaks using the relative retention times given in
Table 1: the resolution,
R, between nefazodone related compound A and nefazodone hydrochloride is not less than 2.0; and the resolution,
R, between nefazodone related compound B and nefazodone hydrochloride is not less than 1.5.
[note—Approximate relative retention times are provided in
Table 1 for informational purposes only.
]
Procedure—
Inject equal volumes (about 10 µL) of the
Standard solution and the
Test solution into the chromatograph, record the chromatograms, and measure the peak responses. Calculate the percentage of individual nefazodone related compounds in the portion of Tablets taken by the formula:
100(rU / rS)(CS / CT)(1/F)
in which
rU is the individual peak response for each nefazodone related compound obtained from the
Test solution; rS is the response of the corresponding peak in the
Standard solution, respectively;
CS and
CT are the concentrations, in mg per mL, of nefazodone hydrochloride in the
Standard solution and the
Test solution, respectively; and
F is the relative response factor obtained from
Table 1. The related compound requirements are listed in
Table 1.
Table 1
| Related Compound |
Relative Retention
Time |
Relative Response
Factor (F) |
Limit (%) |
| Nefazodone related compound A |
1.4 |
1.2 |
0.2 |
| Nefazodone related compound B |
0.9 |
1.0 |
0.2 |
| Any individual unknown impurity |
— |
1.0 |
0.2 each |
| Total known and unknown |
— |
— |
0.5 |
Assay—
Dilute acetic acid—
Prepare a mixture of acetic acid and water (1:1).
Buffer solution—
Dissolve 0.77 g of ammonium acetate in 1 L of water. Add 1.0 mL of triethylamine, and mix well. Adjust with Dilute acetic acid to a pH of 7.10 ± 0.05, and mix.
Mobile phase—
Prepare a filtered and degassed mixture of acetonitrile and
Buffer solution (58:42). Make adjustments if necessary (see
System Suitability under
Chromatography 621).
Assay stock preparation—
Weigh and finely powder not fewer than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 250 mg of nefazodone hydrochloride, based on the label claim, to a 250-mL volumetric flask, add about 125 mL of Mobile phase, and sonicate for about 10 minutes with occasional shaking. Dilute with Mobile phase to volume, and mix to obtain a solution having a concentration of about 1 mg per mL of nefazodone hydrochloride. Pass a portion of this solution through a filter having a 0.45-µm or finer porosity, and use the filtrate, which has a concentration of about 1 mg per mL of nefazodone hydrochloride.
Assay preparation—
Transfer 5.0 mL of Assay stock preparation into a 50-mL volumetric flask. Dilute with Mobile phase to volume, and mix to obtain a solution having a concentration of 0.1 mg per mL of nefazodone hydrochloride.
Chromatographic system (see Chromatography 621)—
The liquid chromatograph is equipped with a 250-nm detector and a 4.6-mm × 25-cm column containing 5-µm L1 packing. The flow rate is about 1.0 mL per minute. The column temperature is maintained at 30
. Inject the
Standard preparation, and record the peak responses as directed for
Procedure: the tailing factor is not more than 2.0; 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. Calculate the quantity, in percent of label claim, of nefazodone hydrochloride (C
25H
32ClN
5O
2·HCl) in the portion of Tablets taken by the formula:
100(CS / CU)(rU / rS)
in which
CS and
CU are the concentrations, in mg per mL, of nefazodone hydrochloride in the
Standard preparation and the
Assay preparation, respectively; and
rU and
rS are the peak areas obtained from the
Assay preparation and the
Standard preparation, respectively.
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