Hanna G M, Lau-Cam C A
Food and Drug Administration, Department of Health and Human Services, New York Regional Laboratory, Brooklyn 11239-1993, USA.
J Pharm Biomed Anal. 1995 Oct;13(11):1313-9. doi: 10.1016/0731-7085(95)01556-z.
A 1H NMR spectroscopic method with chiral shift chelate is presented for the determination of the optical purity of timolol maleate. Optimum experimental conditions were established by studying the interactions 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 spectral changes of the resonance signals for the enantiomeric -C(CH3)3 protons, suitable conditions for quantitative determinations were found when 0.1 molar equivalents of Pr(hfc)3 were complexed with 0.074 M of substrate. Enantiomeric compositions were calculated from the relative intensities of the enantiomeric -C(CH3)3 proton resonances. Based 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.
提出了一种采用手性位移螯合物的1H NMR光谱法来测定马来酸噻吗洛尔的光学纯度。通过研究溶剂（CCl4、CDCl3）、底物浓度以及手性镧系螯合物（Pr(hfc)3、Eu(hfc)3）的类型和浓度之间的相互作用，确定了最佳实验条件。与Eu(hfc)3相比，Pr(hfc)3获得了更大的诱导位移（δδ）和对映体位移差异（δδδ）值，以及更详细的光谱差异。通过监测对映体-C(CH3)3质子共振信号的光谱变化，当0.1摩尔当量的Pr(hfc)3与0.074 M的底物络合时，发现了适合定量测定的条件。对映体组成由对映体-C(CH3)3质子共振的相对强度计算得出。基于对六种合成对映体混合物的分析，所提出方法对(R)-(+)-噻吗洛尔的平均回收率±标准差为加入量的99.5±1.17%。
