DETERMINATION OF THE OPTICAL PURITY OF TIMOLOL MALEATE BY PROTON NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPY WITH A CHIRAL PR(III) SHIFT-REAGENT

A H-1 NMR spectroscopic method with chiral shift chelate is presented for the determination of the optical purity of timolol maleate. Optimu m experimental conditions were established by studying the interaction s of solvents (CCl4, CDCl3), substrate concentration, and the type and concentration of chiral lanthanide chelate (Pr(hfc)(3), Eu(hfc)(3)). Larger induced shift (Delta delta) and enantiomeric shift difference ( Delta Delta delta) values, and more detailed spectral differences were obtained with Pr(hfc)(3) than with Eu(hfc)(3). By monitoring the spec tral changes of the resonance signals for the enantiomeric -C(CH3)(3) protons, suitable conditions for quantitative determinations were foun d when 0.1 molar equivalents of Pr(hfc)(3) were complexed with 0.074 M of substrate. Enantiomeric compositions were calculated from the rela tive intensities of the enantiomeric -C(CH3)(3) proton resonances. Bas ed on the analysis of six synthetic enantiomeric mixtures, the mean +/ -SD recovery of (R)-(+)-timolol by the proposed method was 99.5 +/- 1. 17% of the amount added.