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 11— USP Nadolol RS.

Identification, Infrared Absorption 197M.

Loss on drying 731— Dry it in vacuum at 60 for 3 hours: it loses not more than 2.0% of its weight.

Residue on ignition 281: not more than 0.1%.

Heavy metals, Method II 231: 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 ± 0.1 at 6.3 µm. Record the spectrum from 6 to 9 µm, using mineral oil in the reference beam. Calculate the percentage of racemate A in the portion of Nadolol taken by the formula: in which 0.9 is the average value of (Aa/Ab) in a mixture of racemates A and B (1:1), Aa is the uncorrected absorbance at the wavelength of a maximum absorbance at about 7.90 µm, corresponding to racemate A, and Ab is the uncorrected absorbance at the wavelength of a maximum absorbance at about 8.00 µm, corresponding to racemate B: the content of racemate A is between 40% and 60%.

Chromatographic purity— Prepare the test solution by dissolving about 500 mg of Nadolol in 10.0 mL of a mixture of methanol and chloroform (1:1). Prepare a solution of USP Nadolol RS in a mixture of methanol and chloroform (1:1) containing about 50 mg per mL. [NOTE—This Standard solution is used only to identify the nadolol zone.] Divide a thin-layer chromatographic plate (see Chromatography 621) 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, 100 µL of the Standard solution, two 100-µL portions of the test solution, and 100 µL of 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 2 M ammonium 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 UV light. 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-mL centrifuge tubes, and similarly transfer the silica gel removed from the corresponding area of the blank chromatogram to a third 50-mL centrifuge tube. Remove the silica gel from the combined impurity zones in each chromatogram of the test solution, and transfer to separate 50-mL centrifuge tubes, and similarly transfer the silica gel removed from the corresponding area of the blank chromatogram to a sixth 50-mL centrifuge tube. Add 30.0 mL of alcohol to each of the 2 tubes containing the mixtures from the nadolol zones and to the third tube containing the corresponding portion of the blank mixture, and add 10.0 mL of alcohol to each of the 2 tubes containing the mixtures from the impurity zones and to the sixth tube containing the corresponding portion of the blank mixture. Shake for 60 minutes, and centrifuge to clarify. Concomitantly determine the absorbances of the supernatants at the wavelength of maximum absorbance at about 278 nm, 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 Ai is the average absorbance of the impurity zone eluates corrected for the corresponding blank, and AU is the average absorbance of the nadolol zone eluates corrected for the corresponding blank: not more than 2.0% is found.

Organic volatile impurities, Method IV 467: meets the requirements.

Residual solvents 467: meets the requirements.

Assay—

Expert Committee : (MDCV05) Monograph Development-Cardiovascular

USP29–NF24 Page 1467

Phone Number : 1-301-816-8305