C17H27NO4 309.40

2,3-Naphthalenediol,5-[3-[(1,1-dimethylethyl)amino]-2-hydroxypropoxy]-1,2,3,4-tetrahydro-,cis-.
1-(tert-Butylamino)-3-[(5,6,7,8-tetrahydro-cis-6,7-dihydroxy-1-naphthyl)oxy]-2-propanol [42200-33-9].

Packaging and storage— Preserve in well-closed containers.

USP Reference standards á11ñ— USP Nadolol RS.

Identification,Infrared Absorption á197Mñ.

Loss on drying á731ñ— Dry it in vacuum at 60for 3hours:it loses not more than 2.0%of its weight.

Residue on ignition á281ñ: not more than 0.1%.

Heavy metals,Method IIá231ñ: 0.003%.

Racemate composition— Prepare a mineral oil dispersion of Nadolol,previously dried,adjusting the thickness of the mull to give an absorbance reading of 0.6±0.1at 6.3µm.Record the spectrum from 6to 9µm,using mineral oil in the reference beam.Calculate the percentage of racemate Ain the portion of Nadolol taken by the formula: in which 0.9is the average value of (Aa/Ab)in a mixture of racemates Aand B(1:1),Aais the uncorrected absorbance at the wavelength of a maximum absorbance at about 7.90µm,corresponding to racemate A,and Abis the uncorrected absorbance at the wavelength of a maximum absorbance at about 8.00µm,corresponding to racemate B:the content of racemate Ais between 40%and 60%.

Chromatographic purity— Prepare the test solution by dissolving about 500mg of Nadolol in 10.0mLof a mixture of methanol and chloroform (1:1).Prepare a solution of USP Nadolol RSin a mixture of methanol and chloroform (1:1)containing about 50mg per mL.[NOTE—This Standard solution is used only to identify the nadolol zone.]Divide a thin-layer chromatographic plate (see Chromatography á621ñ)coated with a 0.25-mm layer of chromatographic silica gel mixture,into four equal sections,the first section to be used for the Standard solution,the next two sections to be used for the test solution,and the last section for the blank.Apply,as streaks,100µLof the Standard solution,two 100-µLportions of the test solution,and 100µLof the mixture of methanol and chloroform (1:1)to provide the blank to appropriate sections of the plate,drying each solution as it is applied with a current of cool air.Develop the chromatogram in a solvent system consisting of a mixture of acetone,chloroform,and 2Mammonium hydroxide (8:1:1)until the solvent front has moved about three-fourths of the length of the plate.Remove the plate from the developing chamber,air-dry,and locate the bands by viewing under short-wavelength UVlight.Identify the nadolol zones by comparison of the chromatograms of the test solution with the chromatogram of the Standard solution.Mark the nadolol zones and the separated impurity zones in the chromatograms of the test solution,and the corresponding zones in the blank section of the plate.Remove the silica gel from the nadolol zone in each chromatogram of the test solution,and transfer to separate 50-mLcentrifuge tubes,and similarly transfer the silica gel removed from the corresponding area of the blank chromatogram to a third 50-mLcentrifuge tube.Remove the silica gel from the combined impurity zones in each chromatogram of the test solution,and transfer to separate 50-mLcentrifuge tubes,and similarly transfer the silica gel removed from the corresponding area of the blank chromatogram to a sixth 50-mLcentrifuge tube.Add 30.0mLof alcohol to each of the 2tubes containing the mixtures from the nadolol zones and to the third tube containing the corresponding portion of the blank mixture,and add 10.0mLof alcohol to each of the 2tubes containing the mixtures from the impurity zones and to the sixth tube containing the corresponding portion of the blank mixture.Shake for 60minutes,and centrifuge to clarify.Concomitantly determine the absorbances of the supernatants at the wavelength of maximum absorbance at about 278nm,with a suitable spectrophotometer,using alcohol as the spectrophotometer blank.Calculate the percentage of impurities in the portion of Nadolol taken by the formula: in which Aiis the average absorbance of the impurity zone eluates corrected for the corresponding blank,and AUis the average absorbance of the nadolol zone eluates corrected for the corresponding blank:not more than 2.0%is found.

Organic volatile impurities,Method IVá467ñ: meets the requirements.

Assay—

Expert Committee:(PA5)Pharmaceutical Analysis 5

USP28–NF23Page 1321

Phone Number:1-301-816-8305