UTILIZING NUCLEAR-MAGNETIC-RESONANCE (NMR) SPECTROSCOPY FOR ASSESSINGNADOLOL RACEMATE COMPOSITION

NMR methods were developed for the determination of the racemate compo sition in nadolol racy materials. With high-field instruments (400 MHz or greater) the racemate ratio may be determined by the relative heig hts of the t-butyl peaks, which are well enough resolved for this dete rmination. For lower field spectrometers, the t-butyl peaks are not re solved. An NMR method has been developed which involves preparation of the tribenzoate derivative of the drug. Seven lots of nadolol raw mat erial, as well as several standards, were analysed for their racemate content. Three lots of raw material did not meet the USP limits of 40- 60% for racemate A. Of these, two were granular in appearance and were found to vary markedly in racemate composition in successive analyses . The results for all the materials of uniform content agree Very well with those from the HPLC method, as well as for the USP IR method usi ng the absorbance at the corrected wavelength.