Medical Products Agency, P.O. Box 26, SE-75103 Uppsala, Sweden.
J Pharm Biomed Anal. 2010 Sep 5;52(5):645-51. doi: 10.1016/j.jpba.2010.02.007. Epub 2010 Feb 11.
In quantitative NMR (qNMR) selection of an appropriate internal standard proves to be crucial. In this study, 25 candidate compounds considered to be potent internal standards were investigated with respect to the ability of providing unique signal chemical shifts, purity, solubility, and ease of use. The (1)H chemical shift (delta) values, assignments, multiplicities and number of protons (for each signal), appropriateness (as to be used as internal standards) in four different deuterated solvents (D(2)O, DMSO-d(6), CD(3)OD, CDCl(3)) were studied. Taking into account the properties of these 25 internal standards, the most versatile eight compounds (2,4,6-triiodophenol, 1,3,5-trichloro-2-nitrobenzene, 3,4,5-trichloropyridine, dimethyl terephthalate, 1,4-dinitrobenzene, 2,3,5-triiodobenzoic acid, maleic acid and fumaric acid) were qualified using both differential scanning calorimetry (DSC) and NMR spectroscopy employing highly pure acetanilide as the reference standard. The data from these two methods were compared as well as utilized in the quality assessment of the compounds as internal standards. Finally, the selected internal standards were tested and evaluated in a real case of quantitative NMR analysis of a paracetamol pharmaceutical product.
在定量 NMR（qNMR）中，选择合适的内标物被证明是至关重要的。在本研究中，我们研究了 25 种候选化合物，这些化合物被认为是潜在的内标物，考察了它们提供独特信号化学位移、纯度、溶解度和易用性的能力。我们研究了这些候选内标物在四种不同氘代溶剂（D2O、DMSO-d6、CD3OD、CDCl3）中的（1）H 化学位移（δ）值、归属、多重性和质子数（每个信号），以及它们在四个不同氘代溶剂中的适用性（作为内标物使用）。考虑到这些 25 种内标物的性质，我们选择了最通用的八种化合物（2,4,6-三碘苯酚、1,3,5-三氯-2-硝基苯、3,4,5-三氯吡啶、对苯二甲酸二甲酯、1,4-二硝基苯、2,3,5-三碘苯甲酸、马来酸和富马酸），并使用高纯度的乙酰苯胺作为参考标准，同时使用差示扫描量热法（DSC）和 NMR 光谱对其进行了定性。我们比较了这两种方法的数据，并将其用于评估这些化合物作为内标物的质量。最后，我们对选定的内标物进行了测试和评估，并将其应用于对乙酰氨基酚药物产品的定量 NMR 分析的实际案例中。
