PDF(Pubmed)
Abstract：
Quantitative 1H-NMR became an increasingly important issue in pharmaceutical analytical chemistry. This study used NMR spectroscopy to assay the bronchodilator drug terbutaline sulfate and its pro-drug bambuterol hydrochloride in pure form and pharmaceutical preparations. The technique proceeded using deuterium oxide (D2O) as an 1H-NMR solvent and phloroglucinol anhydrous as an internal standard (IS). Comparatively, to the phloroglucinol signal at 5.9 ppm, the resulting quantitative signals of the studied drugs were corrected. The terbutaline singlet signal at 6.3 ppm was chosen for quantification, while the bambuterol quantitative singlet signal was at 2.9 ppm. The two drugs were rectilinear over the concentration range of 1.0-16.0 mg/mL. LOD values were 0.19 and 0.21 mg/mL while LOQ values were 0.58 and 0.64 mg/mL for terbutaline and bambuterol respectively. The developed method has been validated according to the International Conference of Harmonization (ICH) regarding linearity, accuracy, precision, specificity, and robustness. A greenness profile assessment was applied, and the method proved to be green. The method enables the assay of the two drugs in pure drug and pharmaceutical preparations. The method also enables the assay of the two drugs in the presence of each other; thus, it is considered a stability-indicating method where terbutaline is an acid degradation product of bambuterol.
摘要：
定量1H-NMR成为药物分析化学中越来越重要的问题。这项研究使用NMR光谱法测定了纯净形式的支气管扩张剂药物硫酸特布他林及其前药盐酸班布特罗和药物制剂。该技术使用氧化氘（D2O）作为1H-NMR溶剂，无水间苯三酚作为内标（IS）进行。相对而言,在5.9ppm的间苯三酚信号，校正了所研究药物的定量信号。选择6.3ppm的特布他林单态信号进行定量，而班布特罗定量单态信号为2.9ppm。两种药物在1.0-16.0mg/mL的浓度范围内呈线性关系。特布他林和班布特罗的LOD值分别为0.19和0.21mg/mL，而LOQ值分别为0.58和0.64mg/mL。所开发的方法已经根据国际协调会议(ICH)关于线性度的验证，准确度,精度,特异性，和鲁棒性。应用了绿色轮廓评估，这种方法被证明是绿色的。该方法能够测定纯药物和药物制剂中的两种药物。该方法还能够在彼此存在的情况下测定两种药物；因此，它被认为是一种稳定性指示方法，其中特布他林是班布特罗的酸降解产物。
