(a'' se bue' toe lol hye'' droe klor' ide).
Butanamide, N-[3-acetyl-4-[2-hydroxy-3-[(1-methylethyl)amino]propoxy]phenyl]-, monohydrochloride, (±)-.
(±)-3¢-Acetyl-4¢-[2-hydroxy-3-(isopropylamino)propoxy]-butyranilide monohydrochloride [34381-68-5].
» Acebutolol Hydrochloride contains not less than 98.0 percent and not more than 102.0 percent of C18H28N2O4·HCl, calculated on the dried basis.
Packaging and storage Preserve in tight containers, and store at controlled room temperature.
USP Reference standards 11
B: Prepare a mixture of the Standard preparation and the Assay preparation (1:1), and chromatograph the mixture as directed in the Assay: the chromatogram thus obtained exhibits a single major peak due to acebutolol.
C: It responds to the tests for Chloride 191, when tested as directed for alkaloidal hydrochlorides.
pH 791: between 4.5 and 7.0, in a solution (1 in 100).
Melting range 741: between 140 and 144.
Loss on drying 731 Dry it at 105 for 3 hours: it loses not more than 1.0% of its weight.
Residue on ignition 281: not more than 0.1%.
Heavy metals, Method II 231: 0.002%.
Standard solution Prepare a solution of USP Acebutolol Hydrochloride RS in methanol containing 1.0 mg per mL.
Test solution 1 Prepare a solution of Acebutolol Hydrochloride in methanol containing 10 mg per mL.
Test solution 2 Mix 1 mL of Test solution 1 and 9 mL of methanol.
Reference solution 1 Transfer 3.0 mL of the Standard solution to a 100-mL volumetric flask, dilute with methanol to volume, and mix.
Reference solution 2 Mix 5.0 mL of Reference solution 1 and 10.0 mL of methanol.
Procedure Apply separate 20-µL portions of the Standard solution, Test solution 1, Test Solution 2, Reference solution 1, and Reference solution 2 to a suitable thin-layer chromatographic plate (see Thin-Layer Chromatography under Chromatography 621) coated with a 0.25-mm layer of chromatographic silica gel mixture. Allow the spots to dry, and develop the chromatograms in a solvent system consisting of the upper layer of a mixture of water, butyl alcohol, and glacial acetic acid (50:40:10) until the solvent front has moved about three-fourths of the length of the plate. Remove the plate from the developing chamber, mark the solvent front, and allow the plate to air-dry. Examine the plate under short-wavelength UV light: the chromatograms from Test solution 2 and the Standard solution show principal spots at about the same RF value. No secondary spot in the chromatogram from Test solution 1, excluding the area at the point of application, is more intense than the principal spot obtained from Reference solution 1 (0.3%), and not more than two secondary spots in the chromatogram from Test solution 1 are more intense than the principal spot obtained from Reference solution 2 (0.1%), and the total of all impurities detected in the chromatogram of Test solution 1 is not more than 0.5%.
Mobile phase Prepare a filtered and degassed mixture of methanol, a 0.3% aqueous solution of sodium dodecyl sulfate, and glacial acetic acid (675:325:20). Make adjustments if necessary to achieve a retention time for acebutolol of between 4 minutes and 7 minutes (see System Suitability under Chromatography 621).
Standard preparation Quantitatively dissolve an accurately weighed quantity of USP Acebutolol Hydrochloride RS in water to obtain a solution having a known concentration of about 0.14 mg per mL.
Assay preparation Transfer about 35 mg of Acebutolol Hydrochloride, accurately weighed, to a 250-mL volumetric flask, dilute with water to volume, and mix.
Chromatographic system (see Chromatography 621) The liquid chromatograph is equipped with a 254-nm detector and a 3.9-mm × 30-cm column that contains packing L1. The flow rate is about 2 mL per minute. Chromatograph the Standard preparation, and record the peak responses as directed for Procedure: the column efficiency is not less than 1500 theoretical plates; the tailing factor is not more than 2.5; 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 mg, of C18H28N2O4·HCl in the portion of Acebutolol Hydrochloride taken by the formula:
250C(rU / rS)in which 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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USP35NF30 Page 2026Pharmacopeial Forum: Volume No. 28(4) Page 1063