The nondestructive and high sensitive analysis of a low content of an active pharmaceutical ingredient (API) was a difficult problem, especially in a complex system of pharmaceutical formulations. In this paper, a rapid and no sample preparation method was developed, which used a 1064 nm Raman spectrometer to detect entecavir monohydrate (ETV-H) in Baraclude tablets. Entecavir was a drug approved by FDA for the treatment of chronic hepatitis B and became the first choice in the market. The wavelength selection results displayed that the signal-to-background ratio of the Raman spectrum with 1064 nm excitation wavelength was 14 times that of the commonly used 785 nm wavelength. The partial least squares (PLS) method was used to calibrate concentration models containing 0.1% to 1.0% w/w% ETV-H in calibration set samples. Different preprocessing methods were used to eliminate the background interference and extract more spectral information. Calibration samples were used to choose the best performing model. Then, all the calibration samples combined with the best performing models’ parameters successfully predicted the content of ETV-H in Baraclude tablets. Combining baseline processing and standard normal variate (SNV) with PLS, the model showed a good result with an R² of 0.973, RMSEC of 0.05%, and RMSEP of 0.03% on the spectral region of 1350–1700 cm⁻¹. The limit of detection of this model was 0.17%. These results showed that 1064 nm Raman spectroscopy technology could be an alternative analytical procedure to quantify low-content API in intact tablets.

中文翻译：

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使用1064 nm拉曼光谱仪对Entecavir片剂进行低含量定量

低含量的活性药物成分（API）的无损分析和高灵敏度分析是一个难题，特别是在复杂的药物制剂系统中。本文开发了一种无需样品的快速制备方法，该方法使用1064 nm拉曼光谱仪检测Baraclude片剂中的恩替卡韦一水合物（ETV-H）。恩替卡韦是经FDA批准用于治疗慢性乙型肝炎的药物，并成为市场上的首选。波长选择结果表明，激发波长为1064 nm的拉曼光谱的信噪比为常用785 nm波长的14倍。偏最小二乘（PLS）方法用于校准校准集中样本中包含0.1％至1.0％w / w％ETV-H的浓度模型。使用了不同的预处理方法来消除背景干扰并提取更多光谱信息。校准样品用于选择性能最佳的模型。然后，所有校准样品与性能最佳的模型参数相结合，成功地预测了Baraclude片剂中ETV-H的含量。将基线处理和标准正态变量（SNV）与PLS结合使用，该模型显示出了很好的结果，在1350–1700 cm ^-1的光谱区域上，R ²为0.973，RMSEC为0.05％，RMSEP为0.03％。该模型的检出限为0.17％。这些结果表明，1064 nm拉曼光谱技术可能是定量分析完整片剂中低含量API的替代分析方法。