Penbutolol Sulfate Tablets
» Penbutolol Sulfate Tablets contain not less than 90.0 percent and not more than 110.0 percent of the labeled amount of (C18H29NO2)2·H2SO4.
Packaging and storage—
Preserve in well-closed, light-resistant containers.
USP Reference standards 
11
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11—
USP Penbutolol Sulfate RS 
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Identification, Ultraviolet Absorption 197U—
197U—
Solution:
Sonicate a weighed portion of ground Tablets in sufficient methanol to obtain a solution containing about 0.4 mg of penbutolol sulfate per mL. Filter this solution, and dilute a portion of the filtrate with methanol to obtain a solution containing about 0.06 mg of penbutolol sulfate per mL.
Dissolution 711—
711—
Medium:
water; 900 mL.
Apparatus 2:
50 rpm.
Time:
30 minutes.
Mobile phase—
Dissolve 2 g of ammonium acetate in 250 mL of water, add 750 mL of acetonitrile, mix, and adjust with glacial acetic acid to a pH of 6.0. Filter and degas. Make adjustments if necessary (see System Suitability under Chromatography 621).
621).
Standard solution—
Dissolve an accurately weighed quantity of USP Penbutolol Sulfate RS quantitatively in water to obtain a stock solution having a known concentration of about 0.018 mg per mL. Mix 10.0 mL of this solution and 10.0 mL of acetonitrile, and filter through a filter having a 0.5-µm or finer porosity.
Test solution—
Filter about 30 mL of the solution under test. Mix 10.0 mL of the filtrate and 10.0 mL of acetonitrile, and filter through a filter having a 0.5-µm or finer porosity.
Chromatographic system
(see Chromatography 621)—The liquid chromatograph is equipped with a 272-nm detector, a 4.6-mm × 15-cm column that contains 5-µm diameter packing L10. The flow rate is about 2.5 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 2.5%.
621)—The liquid chromatograph is equipped with a 272-nm detector, a 4.6-mm × 15-cm column that contains 5-µm diameter packing L10. The flow rate is about 2.5 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 2.5%.
Procedure—
Separately inject equal volumes (about 50 µL) of the Standard solution and the Test solution into the chromatograph, and measure the areas of the responses for the penbutolol peaks. Calculate the quantity, in mg, of (C18H29NO2)2·H2SO4 dissolved by the formula:
1800C(rU / rS)
in which C is the concentration, in mg per mL, of USP Penbutolol Sulfate RS in the Standard solution, and rU and rS are the penbutolol peak responses obtained from the Test solution and the Standard solution, respectively.
Tolerances—
Not less than 75% (Q) of the labeled amount of (C18H29NO2)2·H2SO4 is dissolved in 30 minutes.
Chromatographic purity—
Examine the chromatogram of the Assay preparation obtained in the Assay. If an impurity peak is observed at a retention time of 0.8 relative to that of penbutolol, calculate the percentage of that impurity by the formula:
100ri / rs
in which ri is the response of the impurity peak, and rs is the sum of the responses of all of the peaks. If the percentage exceeds 1.2%, perform the following test.
Organic phase, Aqueous phase, Solvent mixture, and Chromatographic system—
Proceed as directed in the test for Chromatographic purity under Penbutolol Sulfate.
Test solution—
Transfer an accurately weighed portion of powdered Tablets, equivalent to about 100 mg of penbutolol sulfate, to a 50-mL volumetric flask, dilute with Solvent mixture to volume, mix, and filter.
Diluted test solution—
Transfer 1.0 mL of the Test solution to a 100-mL volumetric flask, dilute with Solvent mixture to volume, and mix.
Procedure—
Proceed as directed for Procedure in the test for Chromatographic purity under Penbutolol Sulfate. Calculate the percentage of each individual impurity in the portion of Tablets taken by the formula:
ri / rD
in which the terms are as defined therein: not more than 1.2% of any impurity is found.
Assay—
Organic phase
, Aqueous phase, and Mobile phase—Proceed as directed in the Assay under Penbutolol Sulfate.
Standard preparation—
Dissolve an accurately weighed quantity of USP Penbutolol Sulfate RS quantitatively in Mobile phase to obtain a solution having a known concentration of about 0.2 mg per mL.
Resolution solution—
Prepare a solution of 3,4-dimethylbenzophenone in Standard preparation containing about 0.01 mg of 3,4-dimethylbenzophenone per mL.
Assay preparation—
Weigh and finely powder not less than 20 Tablets. Transfer an accurately weighed portion of the powder, equivalent to about 20 mg of penbutolol sulfate, to a 100-mL volumetric flask, dilute with Mobile phase to volume, and mix. Sonicate for about 10 minutes, and filter a portion through a filter having a 0.5-µm or finer porosity, discarding the first 5 mL of the filtrate. Use the clear filtrate as the Assay preparation.
Chromatographic system
(see Chromatography 621)—The liquid chromatograph is equipped with a 270-nm detector and a 4.6-mm × 15-cm column that contains 5-µm diameter packing L1. The flow rate is about 1 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.7 for penbutolol and 1.0 for 3,4-dimethylbenzophenone, and the tailing factor is not more than 1.4, when calculated by the formula:
621)—The liquid chromatograph is equipped with a 270-nm detector and a 4.6-mm × 15-cm column that contains 5-µm diameter packing L1. The flow rate is about 1 mL per minute. Chromatograph the Resolution solution, and record the peak responses as directed for Procedure: the relative retention times are about 0.7 for penbutolol and 1.0 for 3,4-dimethylbenzophenone, and the tailing factor is not more than 1.4, when calculated by the formula:
W0.1 / 2f
in which W0.1 is the width of the peak at 10% of peak height, the resolution, R, between the penbutolol peak and the 3,4-dimethylbenzophenone peak is not less than 5, and the relative standard deviation for replicate injections is not more than 2.0%.
Procedure—
[note—Use peak areas where peak responses are indicated. ] 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. Calculate the quantity, in mg, of (C18H29NO2)2·H2SO4 in the portion of Tablets taken by the formula:
100C(rU / rS)
in which C is the concentration, in mg per mL, of USP Penbutolol Sulfate RS in the Standard preparation, and rU and rS are the penbutolol peak responses 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 4231