采用PXRD、近红外光谱（NIR）、衰减全反射傅里叶变换红外光谱（ATR-FITR）和拉曼固态分析技术结合化学计量学对卡格列净片中低含量多晶型杂质进行定量分析。
Quantitative analysis of low content polymorphic impurities in canagliflozin tablets by PXRD, NIR, ATR-FITR and Raman solid-state analysis techniques combined with stoichiometry.
作者信息
Liu Mingdi, Liu Jichao, Wang Qiuhong, Song Ping, Li Haichao, Wu Songgu, Gong Junbo
机构信息
State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, PR China; College of Chemistry and Chemical Engineering, Qinghai Minzu University, Xining 810007, PR China; Key Laboratory of Resource Chemistry and Eco-environmental Protection in Tibetan Plateau, State Ethnic Affairs Commission, Xining 810007, PR China.
College of Chemistry and Chemical Engineering, Qinghai Minzu University, Xining 810007, PR China; Key Laboratory of Resource Chemistry and Eco-environmental Protection in Tibetan Plateau, State Ethnic Affairs Commission, Xining 810007, PR China.
出版信息
Spectrochim Acta A Mol Biomol Spectrosc. 2023 May 15;293:122458. doi: 10.1016/j.saa.2023.122458. Epub 2023 Feb 16.
Canagliflozin (CFZ) was a commercially new class of anti-diabetic drug, which had various anhydrate crystal forms and two hydrate crystal forms (Canagliflozin hemihydrate (Hemi-CFZ) and Canagliflozin monohydrate (Mono-CFZ) crystal form). Commercially available CFZ tablets' active pharmaceutical ingredient (API) was Hemi-CFZ, which was easy conversion to CFZ or Mono-CFZ under the influence of temperature, pressure, humidity and other factors in tablets processing, storage, and transportation, thus affected bioavailability and efficacy of tablets. Therefore, quantitative analysis low content of CFZ and Mono-CFZ in tablets was essential to control tablets' quality. The main objective of this study was to examine the feasibility of Powder X-ray Diffraction (PXRD), Near Infrared Spectroscopy (NIR), Attenuated Total Reflectance Fourier Transform Infrared Spectroscopy (ATR-FTIR) and Raman for quantitative analysis the low content of CFZ or Mono-CFZ in ternary mixtures. PLSR calibration models for low content of CFZ and Mono-CFZ were established by the solid analysis techniques of PXRD, NIR, ATR-FTIR and Raman combined with various pretreatments (such as Multiplicative Scatter Correction (MSC), Standard Normal Variate (SNV), Savitzky-Golay First Derivative (SG), Savitzky-Golay Second Derivative (SG) and Wavelet Transform (WT)), and the correction models were verified. However, compared with PXRD, ATR-FTIR and Raman, NIR due to its water sensitivity was the most suitable for the quantitative analysis low content of CFZ or Mono-CFZ in tablets. Partial Least Squares Regression (PLSR) model for quantitative analysis low content of CFZ in tablets was as follow: Y = 0.0480 + 0.9928 X, R = 0.9986, LOD = 0.1596 %, LOQ = 0.4838 %, SG + WT pretreated. And that of Mono-CFZ were Y = 0.0050 + 0.9996 X, R = 0.9996, LOD = 0.0164 %, LOQ = 0.0498 %, MSC + WT pretreated and Y = 0.0051 + 0.9996 X, R = 0.9996, LOD = 0.0167 %, LOQ = 0.0505 %, SNV + WT pretreated, respectively. That can be used for quantitative analysis of impurity crystal content in drug production to ensure drug quality.
卡格列净（CFZ）是一类新型的抗糖尿病药物，有多种无水晶体形式和两种水合物晶体形式（卡格列净半水合物（Hemi-CFZ）和卡格列净一水合物（Mono-CFZ）晶体形式）。市售的CFZ片剂的活性药物成分（API）是Hemi-CFZ，在片剂加工、储存和运输过程中，受温度、压力、湿度等因素影响，它很容易转化为CFZ或Mono-CFZ，从而影响片剂的生物利用度和疗效。因此，定量分析片剂中低含量的CFZ和Mono-CFZ对于控制片剂质量至关重要。本研究的主要目的是考察粉末X射线衍射（PXRD）、近红外光谱（NIR）、衰减全反射傅里叶变换红外光谱（ATR-FTIR）和拉曼光谱用于定量分析三元混合物中低含量CFZ或Mono-CFZ的可行性。通过PXRD、NIR、ATR-FTIR和拉曼光谱等固体分析技术结合多种预处理方法（如多元散射校正（MSC）、标准正态变量变换（SNV）、Savitzky-Golay一阶导数（SG）、Savitzky-Golay二阶导数（SG）和小波变换（WT））建立了低含量CFZ和Mono-CFZ的偏最小二乘回归（PLSR）校准模型，并对校正模型进行了验证。然而，与PXRD、ATR-FTIR和拉曼光谱相比，NIR由于其对水的敏感性，最适合定量分析片剂中低含量的CFZ或Mono-CFZ。片剂中低含量CFZ定量分析的偏最小二乘回归（PLSR）模型如下：Y = 0.0480 + 0.9928 X，R = 0.9986，检测限（LOD）= 0.1596%，定量限（LOQ）= 0.4838%，经SG + WT预处理。Mono-CFZ的模型分别为：Y = 0.0050 + 0.9996 X，R = 0.9996，LOD = 0.0164%，LOQ = 0.0498%，经MSC + WT预处理；以及Y = 0.0051 + 0.9996 X，R = 0.9996，LOD = 0.0167%，LOQ = 0.0505%，经SNV + WT预处理。这些模型可用于药物生产中杂质晶体含量的定量分析，以确保药物质量。
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