Pratiwi Destari, Fawcett J Paul, Gordon Keith C, Rades Thomas
Solid State Research Group, School of Pharmacy, University of Otago, Dunedin, New Zealand.
Eur J Pharm Biopharm. 2002 Nov;54(3):337-41. doi: 10.1016/s0939-6411(02)00113-3.
Ranitidine hydrochloride exists as two polymorphs, forms I and II, both of which are used to manufacture commercial tablets. Raman spectroscopy can be used to differentiate the two forms but univariate methods of quantitative analysis of one polymorph as an impurity in the other lack sensitivity. We have applied principal components analysis (PCA) of Raman spectra to binary mixtures of the two polymorphs and to binary mixtures prepared by adding one polymorph to powdered tablets of the other. Based on absorption measurements of seven spectral regions, it was found that >97% of the spectral variation was accounted for by three principal components. Quantitative calibration models generated by multiple linear regression predicted a detection limit and quantitation limit for either forms I or II in mixtures of the two of 0.6 and 1.8%, respectively. This study demonstrates that PCA of Raman spectroscopic data provides a sensitive method for the quantitative analysis of polymorphic impurities of drugs in commercial tablets with a quantitation limit of less than 2%.
盐酸雷尼替丁有两种多晶型物，即I型和II型，二者均用于制造商业片剂。拉曼光谱可用于区分这两种晶型，但将一种多晶型物作为另一种中的杂质进行定量分析的单变量方法缺乏灵敏度。我们已将拉曼光谱的主成分分析（PCA）应用于两种多晶型物的二元混合物以及通过将一种多晶型物添加到另一种的粉末片剂中制备的二元混合物。基于七个光谱区域的吸收测量，发现>97%的光谱变化由三个主成分解释。通过多元线性回归生成的定量校准模型预测，在二者的混合物中，I型或II型的检测限和定量限分别为0.6%和1.8%。本研究表明，拉曼光谱数据的PCA为商业片剂中药物多晶型杂质的定量分析提供了一种灵敏的方法，定量限小于2%。
