Acebutolol Hydrochloride Capsules
» Acebutolol Hydrochloride Capsules contain the equivalent of not less than 90.0 percent and not more than 110.0 percent of the labeled amount of acebutolol (C18H28N2O4).
Packaging and storage— Preserve in tight containers, and store at controlled room temperature.
USP Reference standards 11
USP Acebutolol Hydrochloride RS Click to View Structure
Identification— The retention time of the major peak in the chromatogram of the Assay preparation corresponds to that in the chromatogram of the Standard preparation, as obtained in the Assay.
Dissolution 711
Medium: water; 900 mL.
Apparatus 2: 50 rpm.
Time: 30 minutes.
Procedure— Determine the amount of C18H28N2O4 dissolved by employing UV absorption at the wavelength of maximum absorbance at about 232 nm on filtered portions of the solution under test in comparison with a Standard solution having a known concentration of USP Acebutolol Hydrochloride RS in the same Medium.
Tolerances— Not less than 80% (Q) of the labeled amount of acebutolol (C18H28N2O4) is dissolved in 30 minutes.
Uniformity of dosage units 905: meet the requirements.
Chromatographic purity—
test 1—
Buffer solution— Prepare as directed in the Assay.
Mobile phase— Prepare a filtered and degassed mixture of Buffer solution and methanol (56:44). Make adjustments if necessary (see System Suitability under Chromatography 621).
Diluent— Prepare a mixture of Buffer solution and methanol (50:50).
Standard solution— Transfer about 30 mg of USP Acebutolol Hydrochloride RS, accurately weighed, to a 50-mL volumetric flask. Add about 12 mL of methanol, swirl to dissolve, dilute with Diluent to volume, and mix. Dilute an accurately measured volume of this solution quantitatively, and stepwise if necessary, with Diluent to obtain a solution having a known concentration of about 1.4 µg of USP Acebutolol Hydrochloride RS per mL.
Test solution— Transfer an accurately weighed portion of the contents of 20 opened Capsules, equivalent to about 250 mg of acebutolol, to a 100-mL volumetric flask, add about 25 mL of methanol, and shake by mechanical means for about 15 minutes. Dilute with Diluent to volume, and mix. Centrifuge a portion of this solution, and transfer 10.0 mL of the clear supernatant to a 100-mL volumetric flask. Dilute with Diluent to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 240-nm detector and a 3.9-mm × 15-cm column that contains 4-µm packing L1. The flow rate is about 1 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 6.0%.
Procedure— Separately inject equal volumes (about 35 µL) of the Standard solution, Test solution, and Diluent into the chromatograph, record the chromatograms for about two times the retention time of acebutolol, and measure the responses for all the peaks, disregarding any peaks corresponding to those obtained from the Diluent. Calculate the percentage of each impurity eluting prior to the acebutolol peak in the portion of Capsules taken by the formula:
(336.44/372.89)(0.4C)(ri / rS)
in which 336.44 and 372.89 are the molecular weights of acebutolol and acebutolol hydrochloride, respectively; C is the concentration, in µg per mL, of USP Acebutolol Hydrochloride RS in the Standard solution; ri is the peak response of any individual impurity obtained from the Test solution; and rS is the peak response of acebutolol obtained from the Standard solution: not more than 0.5% of any individual impurity is found.
test 2—
Buffer solution— Prepare as directed in the Assay.
Mobile phase— Prepare a filtered and degassed mixture of Buffer solution and methanol (50:50). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard solution— Transfer about 30 mg of USP Acebutolol Hydrochloride RS, accurately weighed, to a 50-mL volumetric flask. Add about 12 mL of methanol, swirl to dissolve, dilute with Mobile phase to volume, and mix. Dilute an accurately measured volume of this stock solution quantitatively, and stepwise if necessary, with Mobile phase to obtain a solution having a known concentration of about 1.4 µg of USP Acebutolol Hydrochloride RS per mL.
Test solution— Transfer an accurately weighed portion of the contents of 20 opened Capsules, equivalent to about 250 mg of acebutolol, to a 100-mL volumetric flask, add about 25 mL of methanol, and shake by mechanical means for about 15 minutes. Dilute with Mobile phase to volume, and mix. Centrifuge a portion of this solution, and transfer 10.0 mL of the clear supernatant to 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 240-nm detector and a 3.9-mm × 15-cm column that contains 4-µm packing L1. The flow rate is about 1 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 6.0%.
Procedure— Separately inject equal volumes (about 70 µL) of the Standard solution, Test solution, and Mobile phase into the chromatograph, record the chromatograms for about three times the retention time of acebutolol, and measure the responses for all the peaks, disregarding any peaks corresponding to those obtained from the Mobile phase. Calculate the percentage of each impurity eluting after the acebutolol peak in the portion of Capsules taken by the formula:
(336.44/372.89)(0.4C)(ri / rS)
in which 336.44 and 372.89 are the molecular weights of acebutolol and acebutolol hydrochloride, respectively; C is the concentration, in µg per mL, of USP Acebutolol Hydrochloride RS in the Standard solution; ri is the peak response of any individual impurity obtained from the Test solution; and rS is the peak response of acebutolol obtained from the Standard solution: not more than 0.5% of any individual impurity is found. The sum of all individual impurities found in Test 1 and Test 2 is not more than 1.0%.
Assay—
Buffer solution— Dissolve about 2.4 g of sodium 1-decanesulfonate in 1000 mL of water. Adjust with glacial acetic acid to a pH of 3.5.
Mobile phase— Prepare a filtered and degassed mixture of methanol and Buffer solution (60:40). Make adjustments if necessary (see System Suitability under Chromatography 621).
Standard preparation— Dissolve an accurately weighed quantity of USP Acebutolol Hydrochloride RS quantitatively in methanol to obtain a solution having a known concentration of about 0.22 mg per mL. This is equivalent to about 0.2 mg of acebutolol per mL.
Assay preparation— Weigh and mix, as completely as possible, the contents of not fewer than 20 Capsules. Transfer an accurately weighed portion of the powder, equivalent to about 200 mg of acebutolol, to a 200-mL volumetric flask. Add about 180 mL of methanol, and stir by mechanical means for about 30 minutes. Dilute with methanol to volume, and mix. Transfer 5.0 mL of this solution to a 25-mL volumetric flask, dilute with methanol to volume, and mix.
Chromatographic system (see Chromatography 621)— The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm × 15-cm column that contains 5-µm packing L1. The flow rate is about 1 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the tailing factor is not more than 1.5; and the relative standard deviation for replicate injections 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. Calculate the quantity, in mg, of acebutolol (C18H28N2O4) in the portion of Capsules taken by the formula:
(336.44/372.89)(1000C)(rU / rS)
in which 336.44 and 372.89 are the molecular weights of acebutolol and acebutolol hydrochloride, respectively; C is the concentration, in mg per mL, of USP Acebutolol Hydrochloride RS in the Standard preparation; and rU and rS are the acebutolol peak responses obtained from the Assay preparation and the Standard preparation, respectively.
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